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 establishment of hybridomas after fusion of X63-Ag8.653 mouse myeloma cells and splenocytes from BALB/c mice hyperimmunized against human astrocytomas is presented. The animals were primed with 5 X 10(6) chemically modified uncultured or cultured glioma cells. Six weeks after the last immunization step an intrasplenal booster injection was administrated and 3 days later the spleen cells were prepared for fusion experiments. According to the specificity analysis of the generated antibodies 7 hybridoma products (MUC 7-22, MUC 8-22, MUC 10-22, MUC 11-22, MUC 14-22, MUC 15-22 and MUC 2-63) react with gliomas, neuroblastomas and melanomas as well as with embryonic and fetal cells but do not recognize non-neurogenic tumors. The selected monoclonal antibodies (McAbs) of IgG1 and IgG2a isotypes are not extensively characterized but these antibodies have been demonstrated to be reactive with a panel of glioma cell lines with varying patterns of antigen distribution. Using the McAbs described above and a series of cryosections of glioma biopsies and paraffin sections of the same material as well as glioma cultures established from these, variable antigenic profiles among glioma cell populations could be demonstrated. From these results it is evident that there is not only a distinct degree of antigenic heterogeneity among and within brain tumors, but also that the pattern of antigenic expression can change continuously. Some of the glioma associated antigens recognized by the selected antibodies persist after fixation with methanol/acetone and Karnovsky's fixative and probably are oncoembryonic/oncofetal antigen(s). The data suggest that the use of McAbs recognizing tumor associated oncofetal antigens in immunohistochemistry facilitates objective typing of intracranial malignancies and precise analysis of fine needle brain/tumor biopsies in a sensitive and reproducible manner.
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PMID:Monoclonal antibodies against human astrocytomas and their reactivity pattern. 331 7

Case histories of 5 tumor patients treated with natural leukocyte interferon-alpha (IFN-alpha) are presented. One patient with juvenile laryngeal papillomatosis responded well to interferon treatment, but the disease recurred when therapy was withdrawn. Upon reinstitution of treatment, the patient once again responded well. Another patient with myelomatosis also responded well to interferon therapy and in this case, too, the tumor recurred when interferon treatment was withdrawn. Reinstitution of interferon therapy was, however, unsuccessful. One patient with generalized giant cell tumor of bone responded with regression after more than 5 years of interferon treatment. Another patient with pulmonary osteosarcoma metastases, having received irradiation and interferon combination therapy followed by sole interferon treatment, responded well with a lasting stationary radiogram after 6 years of interferon treatment. One patient with malignant glioma, showing signs of tumor growth during the first few months of interferon therapy, eventually responded, and became disease-free after 6 years. The latter 3 patients are continuously receiving interferon therapy although more than 5 years have elapsed since their interferon therapy was initiated. It is suggested that interferon therapy for malignant tumors be given for life (or to progression of disease) in responding patients. Such a concept entails biological implications for interferon therapy in general and for antitumor action of interferons in particular. Other possible clinical schedules should only be constructed within the framework of controlled clinical trials.
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PMID:Does successful interferon treatment of tumor patients require life-long treatment? 347 1

We have recently demonstrated that one of our monoclonal antibodies (MAB's) to glial fibrillary acidic protein (GFAP) recognizes an epitope on this molecule which is to a large degree blocked during fixation with formaldehyde or crosslinking with Dithiobis (Succinimidyl) Propionate (DTSP). This was shown to be due to the crossbinding of a single or a number of proteins to the GFAP and is not due to a change in the epitope on GFAP induced by the fixation itself. In an attempt to produce further MAB's capable of recognizing epitopes on the GFAP molecule available following formaldehyde fixation, we immunized BALB-C mice with cytoskeletal preparations of human glioma cells which contain GFAP where the blocking protein or proteins were crossbound by DTSP or formaldehyde to the GFAP. Following fusion of the spleen lymphocytes to Sp 2/0 myeloma cells we have cloned hybridomas which produce antibodies that recognize GFAP in formaldehyde fixed tissues. This method presents the antigen in its native "fixed" state for the mouse's immune system and avoids the production of MAB's which (although excellent for immunochemical studies) do not recognize any epitopes available on the molecule in question in formaldehyde fixed tissues. Antibodies so produced are of great interest in routine pathology where most tissues are still, unfortunately, undiscriminately fixed in formalin. The results also show that GFAP varies immunologically in different species (i.e. human v. rat/mouse) and confirm that the GFAP of the PNS is immunologically distinct and/or associated with different proteins from that found in the CNS.
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PMID:Monoclonal antibodies to GFAP epitopes available in formaldehyde fixed tissue. 354 74

The uptake of the fluorescent, lysosomotropic weak base acridine orange (AO) by living cells in culture was studied by flow cytofluorometry. A mouse myeloma cell line (SP 2/0), growing in suspension, and an anchorage-dependent human malignant glioma cell line (U-251 MG), brought into suspension by trypsinization, were used. The consequences of trypsinization were also studied using static cytofluorometry. The lysosomal accumulation of AO by myeloma cells growing in suspension was found to be only moderately affected by starvation (i.e. incubation without medium change) for a period of up to five days. Trypsinization of the glioma cells after staining with AO caused pronounced release of the fluorescent dye while trypsinization before staining with AO did not significantly change the average lysosomal concentration of AO. We did, however, notice certain side effects of trypsinization in the form of both increased cellular green fluorescence and greater intercellular variability that reduce the validity of data obtained from cells detached by routine trypsinization. In conclusion, the condition of the lysosomal vacuome of living cultured cells growing in suspension may be studied by flow cytofluorometry after vital staining with the lysosomotropic weak base AO. Anchorage-dependent trypsinized cells, however, yield unsatisfactory results when examined in a flow cytofluorometer system and are better studied while still attached to their substratum, using static cytofluorometry.
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PMID:Flow cytofluorometry of lysosomal acridine orange uptake by living cultured cells. Effect of trypsinization and starvation. 361 27

A monoclonal antibody termed "FR77" was obtained from a hybridoma clone established by fusion between P3x63Ag8.653 mouse myeloma cells and spleen cells of a Fischer F344 rat hyperimmune to syngeneic 9L/R3 glioma cells. Immunoperoxidase staining of various cultured cells showed that FR77 was reactive to both rat and human glioma cells, but was not reactive with other nonglioma cells. Immunohistochemical examination of paraffin-embedded or cryostat-frozen sections of various human tissues revealed that FR77 was strongly reactive with glioblastoma, grade III astrocytoma, and craniopharyngioma; partially reactive with intracerebral primitive neuroectodermal tumor, pineoblastoma, and desmoplastic medulloblastoma; and weakly reactive with low-grade astrocytoma. It was not reactive with other types of brain tumors and normal human tissues tested. The FR77-defined antigen was observed to be predominantly localized in the cytoplasm of antigen-bearing cells as suggested by the immunostaining pattern, but part of it was also expressed on the cell surface of glioma cells as demonstrated by a complement-mediated cytotoxic test. Fractionation of the antigenic component and periodic acid treatment of tumor tissue bearing the FR77-defined antigen indicated that the antigen is of a neutral glycolipid nature and that the antigenic determinant to FR77 is present on its sugar portion.
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PMID:Detection of human glioma-associated antigen by rat monoclonal antibody raised against syngeneic rat glioma cells. 376 Sep 59

The effects of 14AC1 monoclonal antibody (McAb) on 79FR-G-41 rat glioma cells in vitro, on the formation of metastases in lung by antibody coated glioma cells, and on the growth of glioma grafts in BALB/c-nu/nu mice were investigated. The 14AC1 antibodies - isotyped as IgG2a - were obtained from a hybridoma clone established after fusion of X63-Ag8.653 myeloma cells and spleen cells of BALB/c mice hyperimmunized with 79FR-G-41 glioma cells. Antibody treatment of glioma cells in vitro caused evident cell surface alterations and pronounced growth depression of most cells. However, a few tumor cells remained unchanged in morphology and continued to proliferate. Moreover, 14AC1 antibodies drastically reduced lung metastasis by pretreated and i.v. delivered glioma cells. Additionally, 14AC1 antibodies suppressed the growth of transplanted rat gliomas in nude mice as evidenced by a longer latency period and a smaller volume of glioma grafts in treated than in control tumor bearers. Nevertheless, glioma grafts showed accelerated growth after termination of antibody treatment. Further experimental investigation is required in order to identify the precise mechanisms of the effects of McAbs on tumor cells in vitro and in vivo.
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PMID:Growth inhibition of experimental glioma grafts by monoclonal antibody treatment. 377 19

Human monoclonal antibodies were produced by fusing intratumoral lymphocytes from patients with malignant gliomas with a human myeloma line. One antibody was selected for further study after screening for binding activity to glioma cell lines. The patient from whom it was derived developed recurrent glioma. 1 mg of antibody was purified, radiolabelled with 131I, and administered intravenously. The distribution of antibody was determined in the blood, CSF and tumour cyst fluid and compared with that of a control human monoclonal immunoglobulin. Antibody localisation in the tumour was observed and confirmed by external scintiscanning.
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PMID:Localisation of malignant glioma by a radiolabelled human monoclonal antibody. 610 Nov 73

Intratumoral lymphocytes from 12 patients undergoing craniotomy for malignant glioma were fused with a specially derived human myeloma line LICR-LON-HMy2. 71 stable hybridomas were obtained from 5 of the 12 patients. Such hybridomas had a DNA content equal to the sum of that present in lymphocytes and the parent myeloma. The hybridoma supernatants contained human monoclonal immunoglobulins. Glioma-binding activity was detected in 7 out of the 71 supernatants. These results suggest that malignant gliomas contain a population of B lymphocytes which may be involved in host defence against the tumour.
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PMID:Human hybridomas from malignant gliomas. 611 12

The production of hybridomas between X63-Ag8.653 myeloma cells and spleen cells from female BALB/c mice immunized with 79FR-G-41 glioma cells is reported. One hundred and six hybridoma clones were obtained secreting monoclonal antibodies (McAbs) against different target cells. Specificity tests (RIA, micro-ELISA) showed that McAbs produced by three hybridoma clones (13GC1, 14BC1, 14FC3) bound 79FR-G-41 glioma cells but did not react with fibroblasts, kidney and brain cells of newborn F344 rats. From the specificity analysis of two McAbs (13GC1, 14BC1) it is evident that these did not only react with 79FR-G-41 cells but also with other glioma cell lines (78FR-G-219, 78FR-G-284, 78FR-G-299 and 78FR-G-344) established from chemically induced rat brain gliomas. These results suggest, in accordance with the findings in human neuroectodermal tumors, the expression of common reactivity antigens in different brain tumors of glial origin. However, the McAbs obtained against experimental rat glioma cells did not recognize glioma cells derived from spontaneous brain tumors of dog or man. Immunofluorescence and immunoperoxidase tests indicate that there is a remarkable heterogeneity among cells of experimental glioma lines with respect to the expression of glioma associated determinants recognized by McAbs. The fact that only a variable number instead of the totality of tumor cells in any asynchronous and uncloned tumor cell population expresses, at a certain time, recognizable antigenic determinants has to be taken into account, particularly if they are considered to be employing McAbs as carrier molecules for diagnostic and therapeutic purposes.
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PMID:Monoclonal antibodies reactive with glioma cell lines derived from experimental brain tumors. 619

BALB/c mice were immunized with an opioid receptor complex over the period of 1 year. Spleen cells from the mouse, whose serum inhibited opiate binding to rat neural membranes to the greatest extent, were fused with P3-X63-Ag8. 653.3 myeloma cells. By radioimmunoassay (RIA), 32 cell lines have been detected that secrete an antibody to a component of the isolated receptor complex. Antibodies from 2 of the cell lines have an effect on opiate binding to rat neural membranes. One antibody, OR-689.2.4 is an IgM cryoglobulin. This antibody partially inhibited the binding of 3H-dihydromorphine (3H-DHM), 3H-naloxone, 3H-ethylketocyclazocine (3H-EKC), and 3H-D-Ala2, D-Leu5 enkephalin (3H-DADLE) to rat neural membranes. The other antibody, OR-465.3, inhibited the binding of 3H-DHM and 3H-naloxone to rat neural membranes by a maximum of 70%. This antibody also inhibited the binding of 3H-DADLE to neural membranes but, did not affect the binding of this peptide to membranes from the neuroblastoma-glioma hybrid cell line, NG108-15. Work is ongoing to generate monoclonal antibodies specific for each subclass of opioid receptor.
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PMID:Generating monoclonal antibodies to the opioid receptor. 631 52


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