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)

The efficacy of Human 6 IFN (HLIFN) given in a pulse fashion was determined in a phase II study. Ninety-one cancer patients were evaluated (9 myeloma, 12 breast, 14 prostate, 9 melanoma, 4 renal, 6 astrocytoma, 7 ovarian, 9 large bowel, 7 gastric, 14 head and neck). They all had advanced progressive cancer that was resistant to chemotherapy and/or radiotherapy. Patients were treated by intramuscular injection of 6 X 10(2) I.U./m2 for three consecutive days every four weeks. 84 patients were evaluable. Complete clinical response was obtained in 23 patients (4 myeloma, 2 breast, 5 prostate, 1 melanoma, 1 renal, 2 astrocytoma, 2 ovarian, 2 large bowel, 1 gastric, 3 head and neck). Partial responses were observed in 35 patients (3 myeloma, 7 breast, 6 prostate, 4 melanoma, 1 renal, 2 astrocytoma, 3 ovarian, 4 head and neck). Objective responses were related (P less than 0.01) to serum IFN level, with complete and partial responses (P less than 0.01) more commonly seen in those patients whose serum IFN levels at two hours were in the range of 1000 to 1650 I.U./ml. Side effects resulting from pulse IFN were acceptable for this group of patients and consisted of fever, transient chills, malaise and asthenia, and transient thrombocytopenia and leukocytopenia. The extent of fever was directly related (P less than 0.01) to response, and was most elevated in patients who achieved objective responses. IFN administered in a pulse fashion appears to be more effective than daily IFN and merits further evaluation.
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PMID:Clinical results of leukocyte interferon-induced tumor regression in resistant human metastatic cancer resistant to chemotherapy and/or radiotherapy-pulse therapy schedule. 405 26

This paper describes the influence of human fibroblast interferon (IFN-beta) on the cytotoxic activity of natural killer cells (NK) in vitro and in vivo using the blood of healthy donors and myeloma patients. IFN-beta stimulates NK activity against all target cells tested in vitro in a dose-dependent way up to 250% of pretreatment values. At higher IFN concentrations, stimulation returned to baseline values. Stimulation was most pronounced in the lowest lymphocyte to target cell ratio. 1- to 2-h preincubation of effector cells with IFN was enough to achieve maximal stimulation. The effector cells of IFN-treated myeloma-patients, or patients with herpes zoster, showed a clear reduction of toxicity against all cells tested during the first infusion, as compared to the pretreatment values.
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PMID:Effect of human fibroblast interferon on natural killer cell activity: stimulation in vitro and inhibition in vivo. 618 Feb 19

A large number of human haematopoietic cell lines was examined for spontaneous production of interferon. Unconcentrated culture supernatants from 70 out of 71 B-lymphoblastoid cell lines contained considerable amounts of interferon (median titer 22 units per ml); a few lines produced more than 100 units/ml with peak values up to 500 units/ml. In contrast, only one B-lymphoma line out of 18 genuine lymphoma, myeloma, and leukaemia cell lines tested spontaneously produced small amounts of interferon. Following treatment with 5-bromodeoxyuridine (BrdUrd), interferon was produced without further induction in most B-lymphoid cell lines, but not in any of the non-B, non-T, T-lymphoid or myeloid lines examined. Modulation of spontaneous interferon production by chemicals (sodium butyrate, dexamethasone, dimethylsulfoxide, a phorbol ester, and BrdUrd) was studied in more detail in three B-lymphoblastoid and four B-lymphoma cell lines. The patterns of responses observed were different for the action of different chemicals on a given cell line as well as between lymphoblastoid and lymphoma lines in general; furthermore, several lines of evidence suggest that chemicals can differentially influence spontaneous and virus-induced interferon production in an given cell line. The composition of spontaneously produced interferon was analysed using antisera specific for HuIFN-alpha and HuIFN-beta. Interferons produced by untreated as well as BrdUrd-treated lymphoblastoid cells contained more than 95 per cent IFN-alpha, whereas BrdUrd-treated lymphoma cells produced IFN-alpha as well as minor amounts (cell lines Namalwa and NC-37) or even over 90 per cent of IFN-beta (Daudi).
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PMID:Spontaneous production of alpha- and beta-interferon in human lymphoblastoid and lymphoma cell lines. 618 Jul 3

Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
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PMID:Interferon therapy in neoplastic diseases. 618 85

Spleen cells from BALB/c mice, immunized with SDS-acrylamide gel purified human fibroblast interferon (HuIFN-beta) were fused with mouse myeloma cells. Culture fluids from the resulting hybrid cells were screened for HuIFN-beta specificity by the following tests: a solid-phase RIA using partially purified HuIFN-beta, a protein-transfer RIA using electrophoretically resolved and immobilized HuIFN-beta, and a bioassay which tests residual HuIFN-beta activity in the supernatant following immunoprecipitation. Six HuIFN-beta-specific hybridomas were identified; two were capable of partially neutralizing HuIFN-beta activity. All six antibodies bind to the beta 1-IFN polypeptide synthesized in E. coli cells containing a cloned beta 1-IFN DNA sequence. All six monoclonal antibodies were found to be IgG3/kappa.
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PMID:Monoclonal antibodies directed against human fibroblast interferon: characterization and functional studies. 620 71

The present study describes the development of a murine monoclonal antibody (LO-22) directed against 12 native species of HuIFN-alpha. Mice were immunized with purified HuIFN-alpha preparations containing all native species of HuIFN-alpha and spleen cells from immunized mice were fused with P3X63MS1 mouse myeloma cells. Positive hybridoma clones secreting antibodies to HuIFN-alpha were identified by means of a new, extremely sensitive biological semisolid binding assay which was able to disclose positive hybridoma clones consisting of less than 30 hybridoma cells. Antibody affinity columns, made by the LO-22 IgG and monospecific, but polyclonal rabbit IgG, showed identical binding abilities as demonstrated by comparative affinity chromatographies in that the same number of IFN species (12 in total) were found in eluates from parallel experiments. Since LO-22 IgG also recognizes porcine leucocyte interferon, it is suggested that the LO-22 is directed against a common epitope which has been very well conserved in the HuIFN-alpha system, per se. It is suggested that the LO-22 IgG can be used for purification of all HuIFN-alpha proteins--be they recombinantly derived or native--but exerting the common determinant. Preliminary experiments have shown that the LO-22 IgG is highly suitable for ELISA tests.
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PMID:Identification, production, and characterization of murine monoclonal antibody (LO-22) recognizing 12 native species of human alpha interferon. 620 47

In our previous study we found that the ARH 77 human B lymphoblastoid cell line, originating from a patient with multiple myeloma, produced both human interferon-alpha (HuIFN-alpha) and HuIFN-beta after induction with Sendai virus. In order to examine whether IFN-alpha-producing ARH 77 cell clones can be separated from IFN-beta-producing ones, the ARH 77 line was cloned by the soft agar method. Twelve clones chosen at random were examined for IFN production and the antigenic types of IFN produced were determined. All examined clones simultaneously produced both HuIFN-alpha and HuIFN-beta, although the ratio of HuIFN-alpha to HuIFN-beta production was variable among the clones. This result suggests that one lymphoblastoid cell can produce both HuIFN-alpha and HuIFN-beta.
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PMID:The production of interferon-alpha and -beta by cloned human lymphoblastoid cells. Brief report. 631 31

We developed a monoclonal antibody (MAb) specific for human interferon gamma (HuIFN-gamma) by hybridizing cells from the NS-1 myeloma cell line with spleen lymphocytes from BALB/c mice immunized with partially purified HuIFN-gamma. Hybridoma culture supernatants were screened for neutralization of antiviral activity of HuIFN-gamma by the method determining the inhibition of nucleic acid synthesis assay (INAS), employing human fibroblasts infected with encephalomyocarditis virus (EMC). Clones exhibiting neutralization of antiviral activity of HuIFN-gamma were recloned, retested and an MAb with maximum neutralization activity was selected. This MAb was of IgM subclass and was specific for HuIFN-gamma. Antiviral activities either of human leukocyte-derived (HuIFN-alpha) or human fibroblast-derived interferon (HuIFN-beta) were not affected by this monoclonal antibody as determined by the INAS test. The specificity of the MAb for HuIFN-gamma was further confirmed by an indirect immunoprecipitation method, where monoclonal antibody-HuIFN-gamma complexes were immunoprecipitated with rabbit anti-mouse immunoglobulin and remaining IFN activity in the supernatants was determined by virus yield reduction assay. Ammonium sulfate precipitated preparations of this MAb were able to significantly increase (range of 230- to 1300-fold) the virus yield when compared with that obtained in the presence of IFN-gamma. SDS-PAGE analysis revealed that the MAb immunoprecipitates a molecule of Mr = 47 kD under nonreducing conditions. Under reducing conditions, two additional bands of Mr = 26 kD (major band) and Mr = 21 kD (minor band) were observed. A sepharose affinity column was constructed using this MAb and was able to retain approximately 60% of the partially purified HuIFN-gamma preparation applied. Significant amounts of HuIFN-gamma were eluted by increasing the ionic strength and decreasing the pH. HuIFN-alpha and HuIFN-beta were not retained by this column.
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PMID:Mouse monoclonal antibody with specificity for human interferon gamma. 643 82

A single rising dose tolerance trial of rDNA interferon-alpha 2 (IFN-alpha 2) was conducted in eight patients with the diagnoses of non-Hodgkin's lymphoma (NHL), multiple myeloma, and chronic lymphocytic leukemia (CLL). Patients received a total of six i.m. doses at weekly intervals as follows: 1, 3, 10, 30, 60, and 100 x 10(6) IU. Patients were monitored at each dose level for serum IFN activity, anti-IFN antibodies, immunomodulation, clinical toxicity, and response. All patients exhibited clinical toxicity, including fever, chills, fatigue, headache, anorexia, mild-to-moderate leukopenia, nausea, and vomiting. Toxicity was dose-related, with significant side effects occurring in all patients at levels of 10 x 10(6) IU and above and some evidence of tachyphylaxis at higher doses. All side effects, including leukopenia and thrombocytopenia, were of short duration and were resolved within 3-5 days. Fevers, rigors, myalgias, and fatigue were partially alleviated by premedication with acetaminophen or hydrocortisone. Pharmacokinetic data indicated mean peak serum IFN titers greater than 90 at a dose of 10 x 10(6) IU and greater than or equal to 200 at doses greater than or equal to 30 x 10(6) IU 8 h after injection. No anti-IFN antibodies were detected. However, the serum levels achieved at higher doses were not linear, possibly indicating in vivo degradation. Total T cells, B cells, monocytes, and T subsets monitored by flow cytometry with monoclonal antibodies remained essentially constant throughout the trial. Although some patients demonstrated minor augmentations of antibody-dependent cellular cytotoxicity (ADCC) and natural killing (NK) activity at the lowest IFN-alpha 2 doses, the majority of patients demonstrated decreases in NK activity after higher IFN doses. No correlation between immunomodulation and clinical response to IFN was observed. At higher dose levels, the predominant immunomodulatory effect of IFN-alpha 2 was suppression of NK, ADCC, and blastogenic responses to T-cell mitogens and recall antigens. B-cell functional deficits as well as radioresistant T-helper and radiosensitive T-suppressor function assessed in a pokeweed mitogen-driven immunoglobulin secretion assay appeared unaffected by IFN administration. One myeloma patient showed progression and was discontinued after 60 x 10(6) IU. There were four patients (3 NHL, 1 myeloma) who achieved partial remission (greater than or equal to 50% tumor reduction) and three (1 CLL, 2 NHL) who showed objective tumor responses of less than 50%. These data suggest that rDNA IFN-alpha 2 is well-tolerated and may have significant antitumor activity against lymphoproliferative malignancies. Clin
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PMID:Immunomodulation by recombinant interferon-alpha 2 in a phase I trial in patients with lymphoproliferative malignancies. 660 23

Clonogenic tumor cells from fresh biopsies of human cancers were cultivated in vitro and tested for sensitivity by continuous exposure to pharmacologically achievable concentrations of either of two highly purified human leukocyte interferon subtypes (IFN-alpha A and IFN-alpha D) prepared by recombinant DNA methods. The interferons were compared on a weight basis at concentrations of 0.4 and 4.0 ng/ml (equivalent to 80 and 800 units of interferon activity for IFN-alpha A and 2.0 and 20 units for IFN-alpha D). Inhibition of tumor colony-forming units (50% of control or less) was observed in 38.1% of the 273 tumors tested against IFN-alpha A, and in 16% of the 71 tumors tested against IFN-alpha D. Of the tumor types with at least ten samples tested against IFN-alpha A, the percentage of cases exhibiting inhibition was as follows: melanoma (51.7%), lung cancer (50%), myeloma (33.4%), ovarian cancer (33.9%), sarcoma (33.3%), adenocarcinoma of unknown primary (30.4%), breast cancer (28%), acute leukemia (30.8%), and renal cancer (23%). More marked inhibition (30% of control or less) was observed in 18.7% of all tumors tested against IFN-alpha A. Of 60 melanomas tested, 18 (30%) exhibited marked in vitro inhibition of growth with IFN-alpha A. Although a smaller number of tumors (71) were tested against IFN-alpha D on a weight basis, it appeared, in general, to be slightly less active than IFN-alpha A (p less than 0.01), and only 8% of tumors tested exhibited marked inhibition over the same dosage range of interferon. Comparison of the dose-response curves for the 68 tumors tested simultaneously against both interferons did not reveal marked interpatient differences in the inhibition curves, although IFN-alpha D was slightly less active overall. Tumors exhibiting at least 50% inhibition of tumor colony formation also proved to be sensitive to a significantly larger number of cytotoxic drugs (tested simultaneously) than the tumors not inhibited with interferon (p less than 0.0001 for IFN-alpha A). We conclude that the in vitro clonogenic assay may aid in targeting tumor types most likely to exhibit interferon sensitivity and assist in case selection for entry into clinical trials with cloned interferons.
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PMID:Effects of cloned human leukocyte interferons in the human tumor stem cell assay. 668 47


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