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)

Monoclonal antibodies ( MCAs ) have been derived from a fusion of P3-NS1/1-Ag 4-1 (NS1) myeloma cells and splenocytes immunized to human glioma cell line D-54 MG. MCAs 2F3 , 4C7 , and 5B7 were analyzed by cell surface radioimmunoassay (CS-RIA), quantitative absorption, indirect immunofluorescence, and peroxidase-anti-peroxidase (PAP) immunohistology of unfixed tissue samples. MCA 2F3 exhibits the most highly restricted pattern of reactivity we have observed, reacting only with 5/12 glioblastoma cell lines and 1/4 fetal skin lines by CS-RIA, and to 9/11 glioblastoma tissue samples by PAP and absorption analysis; this MCA is totally nonreactive with melanomas, neuroblastomas, meningiomas, and control non-central nervous system tumors, and to adult and fetal tissues including brain, thymus, spleen, liver, lung, heart, gut, skin, and muscle by PAP analysis. MCAs 4C7 and 5B7 demonstrate neuroectodermal tumor cross-reactivity profiles, reacting with either melanomas ( 5B7 ) or melanomas and neuroblastomas ( 4C7 ); both are reactive with fetal skin, brain, and thymus of less than or equal to 16 weeks of gestational age. Other than this latter fetal antigen reactivity, these MCAs share the same negative reactivity profile described above for MCA 2F3 . Data from experiments using control or 0.02% EDTA-treated confluent cell monolayers of D-54 MG as antibody absorbents showed that the antigens detected are present in the extracellular matrix material remaining following cell removal. The data presented here establish that these highly restrictive anti-human glioma cell line MCAs are expressed in primary human gliomas; that the markers defined are developmental in nature, in that they are expressed by human fetal tissue, but not by adult tissue; and that in conjunction with previously characterized specificities, these markers of antigenic heterogeneity will be valuable in model system studies of therapeutic response heterogeneity.
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PMID:Characterization of three restricted specificity monoclonal antibodies raised against the human glioma cell line D-54 MG. 637 21

The hybridoma technique was used to generate monoclonal antibodies against a wide spectrum of melanoma-associated surface antigens. Mice were immunized against the human melanoma lines Mel A-375, SK Mel-25, and Mel S-5 (subclone of SK Mel-25), which differ with respect to a number of biological and biochemical properties. Spleen cells were fused with P3 X 63-AG8.653 myeloma cells. Twenty hybridomas producing antibodies that were negative on platelets, leukocytes, and monocytes but positive on melanoma cells were isolated and recloned. The specificity of antibodies was investigated on 30 human melanoma and nonmelanoma lines. Five groups of antibodies could be distinguished by their reactivity (1) with few melanoma lines and embryonic fibroblasts; (2) with melanoma, neuroblastoma, and teratoma; (3) with melanoma, neuroblastoma, glioblastoma, teratoma, and carcinoma; (4) with melanoma, teratoma, and carcinoma; and (5) with melanoma, neuroblastoma, teratoma, glioblastoma, carcinoma, embryonic fibroblasts, and B-lymphoblastoid cells. The antigen expression was qualitatively and quantitatively different from cell line to cell line. No evidence for melanoma-specific antigens was found. Eight antibodies were isolated detecting phenotypic differences on sublines of SK Mel-25.
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PMID:Detection of phenotypic differences on human malignant melanoma lines and their variant sublines with monoclonal antibodies. 655 61

Monoclonal antibodies against a human plasminogen activator of M(r) approximately 52,000 (HPA52) were derived by immunization of mice with an impure preparation of the enzyme (urokinase), subsequent hybridization of spleen cells with NSI-Ag4/1 myeloma cells, and cloning of the hybridomas. Selection of mice for hybridization and screening of hybridomas were based solely on direct inhibition of an enzymatic assay of the plasminogen activator with the impure enzyme preparation. A cloned hybridoma produced IgG1 antibodies that bound to and inhibited the enzymatic activity of HPA52 irrespective of whether the HPA52 was derived from urokinase or from human glioblastoma cells, whereas there was no inhibition of or binding to a plasminogen activator of M(r) approximately 70,000 from human melanoma cells or a plasminogen activator of M(r) approximately 36,000 that is a degradation product of HPA52 and present in urokinase. Nor did the anti-HPA52 IgG1 inhibit a murine plasminogen activator of M(r) approximately 48,000 derived from sarcoma virus-transformed cells. By using affinity chromatography with columns of anti-HPA52 IgG1 bound to Sepharose, HPA52 was purified from urokinase to homogeneity as evaluated by NaDodSO(4)/polyacrylamide gel electrophoresis. This study demonstrates that inhibitory monoclonal antibodies against enzymes can be derived with the sole use of impure enzyme preparations and shows how such antibodies subsequently can be used for enzyme purification.
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PMID:Monoclonal antibody that specifically inhibits a human Mr 52,000 plasminogen-activating enzyme. 680 14

Within the Special Research Group of Department of Health and Welfare, seven research subgroups which are testing different types of interferon supplied from each seven companies are organized at the time of October 1982. Out of these subgroups, two groups, Toray company group (IFN-beta) and Sumitomo company group (HLBI-alpha), have made clinical trials on 123 cases and 120 cases respectively. Other groups are still under preparation. 6 cases with complete response and 23 cases with partial response by IFN-beta, and 0 cases with complete response and 13 cases with partial response by HLBI-alpha are observed. Over all responded disease are such as glioblastoma, medulloblastoma, melanoma and cutaneous T-cell lymphoma with local injection, and hypernephroma, bladder carcinoma, medulloblastoma, multiple myeloma, and adult T-cell leucaemia with systemic administration.
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PMID:[Current status and problems of cancer treatment with interferon]. 687 30

There are three types of interferons (IFN), alpha, beta and gamma. IFN-alpha is produced in the leukocytes infected with virus, while IFN-beta is from fibroblasts infected with virus. IFN-gamma is induced by the stimulation of sensitized lymphocytes with antigen or non-sensitized lymphocytes with mitogens. It is believed that IFN-alpha and beta originated from the same ancestral gene, whereas IFN-gamma did not. IFN has not only an antiviral activity, but also various kinds of biological activities including cell growth inhibition, immunosuppressive effects, enhancement of macrophage, natural killer (NK) cell, killer (K) cell and neutrophil functions, and cell differentiation-inducing activity. IFN also shows the antitumor activity resulting from the integration of the above-mentioned biological activities. IFN is also deeply involved in the pathogenesis of various diseases, e.g., collagen diseases such as SLE and rheumatoid arthritis, insulin-dependent diabetes mellitus, fulminant hepatitis, severe pancreatitis, nephritis, multiple sclerosis, allergic diseases, and atherosclerosis. At present, IFN is clinically used in therapy against virus infections such as hepatitis B and C, and for malignancies such as renal cell carcinoma, multiple myeloma, malignant melanoma, glioblastoma, skin cancers, malignant lymphoma and chronic myelogenous leukemia.
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PMID:[Interferon-alpha, beta, gamma]. 799 28

Rapid growth of a glioblastoma during therapy for multiple myeloma is reported. A 53-year-old man was admitted to our hospital with a right costal tumor, which was resected. The diagnosis was plasmocytoma. Urine protein electrophoresis showed a monoclonal peak in the region of gamma-globulin, and examination of the bone marrow revealed 17.8% of atypical plasma cells. Brain magnetic resonance (MR) imaging detected two small lesions, but these could not be identified as brain tumor. He received chemotherapy (melphalan 10 mg/day and predonin 30 mg/day for 4 days) and was discharged. Two weeks after discharge, he was readmitted because of left hemiparesis. T1-weighted MR imaging showed two large hypointense lesions in the right frontal lobe, with ring-like enhancement following Gd-DTPA infusion. 1H-MR spectroscopy showed typical findings of tumor with increased choline and lactic acid peaks. 201Tl SPECT revealed high accumulation in both early and delayed images. Right carotid angiography showed a hypervascular tumor with venous filling and mass effect. The lesions were resected via right frontal craniotomy, followed by intraoperative radiation and placement of an Ommaya reservoir. Histological examination showed the tumors were glioblastoma. The brain between the tumors also showed the typical appearance of glioblastoma, suggesting that the lesions were continuous. Postoperatively, the patient's left hemiparesis disappeared. He received local irradiation and chemotherapy and was then discharged. Coexistence of glioblastoma and multiple myeloma is rare. The cause may be genetic abnormality, but immunodeficiency due to multiple myeloma, surgical damage, or chemotherapy may have contributed to the rapid growth of the glioblastoma.
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PMID:[Rapid growth of glioblastoma during therapy for multiple myeloma: case report]. 974 4

Among the 25 bis(cyclopentadienyl)vanadium(IV) and 14 oxovanadium(IV) compounds synthesised and evaluated for anticancer activity, bis(4,7-dimethyl-1,10-phenanthroline) sulfatooxovanadium(IV) (metvan) was identified as the most promising multitargeted anticancer vanadium complex with apoptosis-inducing activity. At nanomolar and low micromolar concentrations, metvan induces apoptosis in human leukaemia cells, multiple myeloma cells and solid tumour cells derived from breast cancer, glioblastoma, ovarian, prostate and testicular cancer patients. It is highly effective against cisplatin-resistant ovarian cancer and testicular cancer cell lines. Metvan is much more effective than the standard chemotherapeutic agents dexamethasone and vincristine in inducing apoptosis in primary leukaemia cells from patients with acute lymphoblastic leukaemia, acute myeloid leukaemia or chronic acute myeloid leukaemia. Metvan-induced apoptosis is associated with a loss of mitochondrial transmembrane potential, the generation of reactive oxygen species and depletion of glutathione. Treatment of leukaemia cells from acute lymphoblastic leukaemia, acute myeloid leukaemia and chronic acute myeloid leukaemia patients with metvan inhibits the constitutive expression as well as the gelatinolytic activities of matrix metalloproteinase-9 and -2. Treatment of human malignant glioblastoma and breast cancer cells with metvan at concentrations > 1 microM is associated with a nearly complete loss of the adhesive, migratory and invasive properties of the treated cancer cell populations. Metvan shows favourable pharmacokinetics in mice and does not cause acute or subacute toxicity at the dose levels tested (12.5 - 50 mg/kg). Therapeutic plasma concentrations > or = 5 microM, which are highly cytotoxic against human cancer cells, can be rapidly achieved and maintained in mice for at least 24 h after intraperitoneal bolus injection of a single 10 mg/kg non-toxic dose of metvan. Metvan exhibits significant antitumour activity, delays tumour progression and prolongs survival time in severe combined immunodeficient mouse xenograft models of human malignant glioblastoma and breast cancer. The broad spectrum anticancer activity of metvan together with favourable pharmacodynamic features and lack of toxicity warrants further development of this oxovanadium compound as a new anticancer agent. Metvan could represent the first vanadium complex as an alternative to platinum-based chemotherapy.
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PMID:Metvan: a novel oxovanadium(IV) complex with broad spectrum anticancer activity. 1245 42

Motexafin gadolinium [gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120] is a radiosensitising agent developed for use in cancer therapy. It is cytotoxic in haematological malignancies by selectively localising in cancer cells that have high rates of metabolism. Motexafin gadolinium inhibits cellular respiration resulting in the production of reactive oxygen species and inducing apoptosis. It is being developed by Pharmacyclics in the US. Bulk motexafin gadolinium is supplied to Pharmacyclics by the US company, Celanese, through a manufacturing and supply agreement between the two companies. In June 2003, at the 39th Annual Meeting of the American Society of Clinical Oncology (ASCO-2003), the importance of having an agent for the treatment of brain metastases from lung cancer was highlighted. Results of a phase III study were presented that showed that motexafin gadolinium treatment was associated with a delay in time to neurological and neurocognitive progression in lung cancer patients. This was an important finding, as 46.6% of lung cancer patients already have brain metastases at the time of initial diagnosis, compared with only 2.7% of breast cancer patients. Brain metastases are also often the only site of metastatic disease in patients with lung cancer. In December 2002, Pharmacyclics began a phase III trial of motexafin gadolinium in patients with brain metastases (brain cancer in phase table) from lung cancer in the US, Europe, Canada and Australia. The trial is known as the Study of neurologic progression with Motexafin gadolinium And Radiation Therapy (SMART) and will compare whole-brain irradiation with whole-brain irradiation plus motexafin gadolinium in 550 patients. The primary efficacy endpoint is time to neurological progression and the secondary endpoints are survival and neurocognitive function. In January 2003, the US FDA completed its Special Protocol Assessment (SPA) of the SMART trial with a positive result and by June 2003, enrollment had begun. In addition, phase I trials are underway in children with intrinsic pontine glioma and adults with head and neck, lung and pancreatic cancers. A phase II trial is also being conducted in the US in patients with glioblastoma multiforme. Enrollment in this trial has been completed and preliminary results have been reported. Pharmacyclics has completed enrollment and follow-up of adults in its pivotal phase III trial of motexafin gadolinium as a radiation sensitiser for the treatment of brain metastases. The trial was conducted at 35 centres in Europe, Canada and the US. Full results from this initial phase III trial were presented at the annual meeting of the American Society of Clinical Oncology (ASCO) in Orlando, Florida, USA, held in May 2002. Pharmacyclics also announced in October 2002, at the 44th Annual Meeting of the American Society for Therapeutic Radiology and Oncology (ASTRO), that motexafin gadolinium significantly prolonged time to neurological progression when added to whole brain radiation therapy and reduced the number of deaths in patients with brain tumour. Pharmacyclics announced in September 2000 that it has initiated two NCI-sponsored phase I trials conducted under a Cooperative Research and Development Agreement (CRADA) between Pharmacyclics and the NCI. The first trial, conducted in patients with stage IIIA non-small cell lung cancer, was designed to determine the safety of two different dosing regimens of motexafin gadolinium during preoperative radiotherapy after induction chemotherapy. The second study was designed to examine the use of motexafin gadolinium in combination with stereotactic Gamma Knife radiosurgery in patients with primary glioblastoma mutiforme. Two phase I clinical trials have also been conducted for the treatment of newly diagnosed glioblastoma multiforme at the UCLA Jonsson Comprehensive Cancer Center, USA. These phase I studies were sponsored by the NCI and were conducted under a CRADA with the NCI. Pharmacyclics has also completed multicentre US phase II clinical trials of motexafin gadolinium fin gadolinium in patients with metastatic tumours of the brain who require whole brain radiotherapy. Motexafin gadolinium is in a phase II trial in patients with lymphomas and multiple myeloma in the US.
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PMID:Motexafin gadolinium: gadolinium (III) texaphyrin, gadolinium texaphyrin, Gd-Tex, GdT2B2, PCI 0120. 1472 95

Activation of the signaling transduction pathways mediated by oncostatin M (OSM) requires the binding of the cytokine to either type I OSM receptor (leukemia inhibitory factor receptor/gp130) or to type II OSM receptor (OSMR/gp130). In the present work we have developed an enzyme-linked immunosorbent assay detecting a soluble form of OSMR (sOSMR) secreted by glioblastoma, hepatoma, and melanoma tumor cell lines. sOSMR was also present in sera of healthy individuals, with increased levels in multiple myeloma. Molecular cloning of a corresponding cDNA was carried out, and it encoded for a 70-kDa protein consisting of a half cytokine binding domain containing the canonical WSXWS motif, an immunoglobulin-like domain, and the first half of a second cytokine binding domain with cysteines in fixed positions. Analysis of the soluble receptor distribution revealed a preferential expression in lung, liver, pancreas, and placenta. sOSMR was able to bind OSM and interleukin-31 when associated to soluble gp130 or soluble interleukin-31R, respectively, and to neutralize both cytokine properties. We have also shown that OSM could positively regulate the synthesis of its own soluble receptor in tumor cells.
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PMID:Molecular and functional characterization of a soluble form of oncostatin M/interleukin-31 shared receptor. 1702 86

Antigens expressed on malignant cells in the absence of significant expression on normal tissues are highly desirable targets for therapeutic antibodies. CD70 is a TNF superfamily member whose normal expression is highly restricted but is aberrantly expressed in hematologic malignancies including non-Hodgkin lymphoma (NHL), Hodgkin disease, and multiple myeloma. In addition, solid tumors such as renal cell carcinoma, nasopharyngeal carcinoma, thymic carcinoma, meduloblastoma, and glioblastoma express high levels of this antigen. To functionally target CD70-expressing cancers, a murine anti-CD70 monoclonal antibody was engineered to contain human IgG1 constant domains. The engineered antibody retained the binding specificity of the murine parent monoclonal antibody and was shown to induce Fc-mediated effector functions including antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and antibody-dependent cellular phagocytosis in vitro. Further, administration of this antibody significantly prolonged survival of severe combined immunodeficient (SCID) mice bearing CD70+ disseminated human NHL xenografts. Survival of these mice was dependent upon the activity of resident effector cells including neutrophils, macrophages, and natural killer (NK) cells. These data suggest that an anti-CD70 antibody, when engineered to contain human IgG1 constant domains, possesses effector cell-mediated antitumor activity and has potential utility for anticancer therapy.
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PMID:Engineered anti-CD70 antibody with multiple effector functions exhibits in vitro and in vivo antitumor activities. 1703 22


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