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)

A monoclonal antibody, KM10 (IgG1) was produced by fusing spleen cells from a human gastric cancer cell (MKN45)-primed BALB/c mouse with the murine myeloma cell line X63-Ag8-653. The antibody reacted strongly with the plasma membrane of human gastrointestinal carcinoma. Sections of the malignant and benign tissues were tested with immunoperoxidase. All of 10 (100%) large intestinal cancers, 26 of 31 (84%) gastric cancers, 5 of 7 (71%) pancreatic cancers and all of 3 (100%) ampullary cancers reacted positively. Moderate or weak reactivity was observed with normal human tissues, hepatoma and carcinomas of mammary, thyroid and adrenal glands. According to a study of the distribution of 125I-labeled KM10 in nude mice bearing human gastric cancer, KM10 selectively localized in tumor tissue rather than normal tissue. Whole body autoradiography also supported such a selective distribution. Destruction of antigenic properties by pronase digestion demonstrated its protein nature and by Western blot analysis, it was identified as a protein with an Mr of 180-200 kd. KM10-adriamycin (ADM) conjugate was prepared via an oxidized dextran bridge and this immunoconjugate retained the binding activity against human gastric cancer. MKN45 cells were inoculated subcutaneously into athymic mice and intravenous treatment was begun when the tumor became measurable. A dose-dependent antitumor activity was observed in vivo with KM10-ADM conjugate, while this conjugate was less toxic than free ADM.
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PMID:A monoclonal antibody, KM10 reactive with human gastrointestinal cancer and its application for immunotherapy. 314 6

People living in the industrial society of today are unavoidably exposed to low-energy electromagnetic (EM) radiation. The potential risk to human health of such exposure has received much study. In this regard, numerous epidemiological studies have linked exposure to low-energy EM fields to increased cancer risk. We investigated the ability of low-energy 60-Hz EM fields to alter the activity of ornithine decarboxylase (ODC) in a number of established cell lines. The activity of ODC, the controlling enzyme in polyamine biosynthesis, has been shown to be elevated in growing cells or tissues and during the process of tumor promotion. A 1-h exposure to a 60-Hz EM field of an intensity of 10 mV/cm produced a 5-fold increase in ODC activity in human lymphoma CEM cells and a 2- to 3-fold increase in mouse myeloma cells (P3) relative to the unexposed cultures. Depending upon the cell type, ODC activity increased during the 1-h exposure period and remained elevated for several hours after the field exposure ended. In another series of experiments, fields of an intensity as low as 0.1 mV/cm for a 1-h period produced a 30% increase in the activity of ODC in Reuber H35 hepatoma cells grown in monolayer culture. In the H35 cells, continuous exposure to the 60-Hz EM field (10 mV/cm) for periods of 2 and 3 h resulted in either no increase in ODC activity (2 h) or a decrease in enzyme activity (3 h) compared to the unexposed control cultures. The data is discussed in relation to possible molecular mechanisms of field-cell interaction, the importance of the exposure intervals altering cellular ODC activity and the potential ability of 60-Hz EM fields to serve as a tumor promoting stimulus.
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PMID:The effects of low-energy 60-Hz environmental electromagnetic fields upon the growth-related enzyme ornithine decarboxylase. 365 76

The rat albumin promoter inserted in adenovirus directs transcription in human and rodent hepatoma cells and in rodent hepatocytes (Friedman et al. 1986) and Babiss et al. (1986) but not in HeLa cells or myeloma cells. The nucleotides between -43 and -156 of the RNA start site of the rat albumin gene are required for this cell-specific expression. Protein binding studies (footprints, exonuclease III stops, and gel shifts) all indicate specific interaction in the -80 to -130 region of the gene with factors present in nuclear extracts of hepatocytes and hepatomas, but also from extracts of other cells that do not express the albumin gene. To observe albumin promoter binding, a smaller amount of extract of liver cell nuclei was required compared to extracts of HeLa cell or kidney cell nuclei. In addition, the various tests of DNA-protein interaction did not give qualitatively identical results with extracts from different cells. However, it seems clear that factors are present in several cell types where albumin genes are inactive that will bind to those DNA sequences demonstrated to be necessary for cell-specific expression of this gene. These factors could either be similar but nonidentical factors or the same factors that are modified differently in different cell types.
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PMID:Factors that interact with the rat albumin promoter are present both in hepatocytes and other cell types. 367 23

PSK is a protein-bound polysaccharide prepared from cultured mycelium of the Basidiomycete Coriolus versicolor. Effects of PSK on the immunologic responsiveness in tumor-bearing animals were investigated using syngeneic or allogeneic tumors in mice (Lewis lung carcinoma, B16 melanoma, Meth A fibrosarcoma, adenocarcinoma 755, X5563 plasmacytoma, colon 26, MOPC 31C myeloma, sarcoma 180 and Ehrlich carcinoma), rats (BC47 bladder carcinoma, Walker 256 sarcoma and AH7974 hepatoma), hamsters (HA-1T tumor and RPMI 1846 melanoma), guinea pigs (line-10 hepatoma) and rabbit (VX2 and VX7 tumor). Oral or intraperitoneal administration of PSK restored the depressed delayed hypersensitivity against sheep erythrocytes to a normal level in these tumor-host systems. Also, oral administration of PSK lowered the activity of immunosuppressive substances in the serum of tumor-bearing animals. These results suggest that PSK exhibits antitumor effects by restoring the depressed immunologic responsiveness in tumor-bearing animals.
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PMID:[Restoration of immunologic responsiveness by PSK in tumor-bearing animals]. 378 58

Four monoclonal antibodies to MH134 murine syngeneic hepatoma cells, 3H1, 7C2, 11G2, and 12A2, were produced by hybridomas constructed by fusing P3-X63-Ag8-U1 murine myeloma cells with spleen cells of a C3H/HeN mouse immunized with the syngeneic tumor cells. Immunodiffusion analysis with rabbit anti-mouse immunoglobulin antisera showed that 3H1, 7C2, 11G2, and 12A2 are IgG2a, IgM, IgG1, and IgG2a, respectively. Enzyme-linked immunosorbent assay using cells of five syngeneic tumor lines, MH134, MM102, MM46, MM48, and X5563, and lymph node cells of C3H/HeN and C57BL/6 mice showed that 3H1 specifically bound to MH134 tumor cells, whereas 7C2, 11G2, and 12A2 reacted not only with MH134 but also with MM102 and MM46 tumor cells. None of these monoclonal antibodies bound either to cells of MM48 or X5563 tumor lines or to normal lymph node cells. These results strongly suggest that MH134 tumor cells display at least two kinds of tumor-associated antigens on their cell surfaces: one is expressed uniquely by MH134 tumor cells, which are recognized by 3H1; the other is commonly shared by MH134, MM102, and MM46 tumor cells, which are determined by the other three antibodies. 3H1, 11G2, and 12A2 but not 7C2 were found to be able to induce antibody-dependent cellular cytotoxicity (ADCC) against MH134 tumor cells. Target specificity of ADCC induced by these monoclonal antibodies was identical with that seen in enzyme-linked immunosorbent assay. 3H1, 7C2, and 12A2 but not 11G2 exhibited complement-dependent cytotoxicity, showing the same specificity in target cell lysis as that seen in enzyme-linked immunosorbent assay or ADCC. Pretreatment of MH134 tumor cells with 7C2 inhibited ADCC of both 11G2 and 12A2. Pretreatment of the tumor cells with 11G2 inhibited complement-dependent cytotoxicity of both 7C2 and 12A2. Neither ADCC nor complement-dependent cytotoxicity of 3H1 was inhibited by the pretreatment of the cells with 7C2 or 11G2. These results strongly suggest that tumor-associated antigens recognized by 3H1 are located apart from that recognized by 7C2, 11G2, and 12A2 and that the binding sites of the latter three antibodies are closely associated with, or identical with, each other in the tumor-associated antigen. The ability of 12A2 to induce ADCC against MH134 tumor cells was significantly stronger than that of 3H1 or 11G2.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Murine tumor cell lysis by antibody-dependent macrophage-mediated cytotoxicity using syngeneic monoclonal antibodies. 397 34

The study was prompted by the apparent detection of insulin antibodies in a black patient with HCC and recurrent hypoglycemia who had never received insulin. It consisted of two parts. Initially the sera of 30 individuals (six normoglycemic HCC patients, three with HCC and recurrent hypoglycemia, 11 patients with noncancerous liver diseases, and 10 healthy black controls) were analyzed for the presence of insulin (and glucagon) antibodies by precipitating the bound, labeled hormone with ethanol and also by the technique of radioimmunoelectrophoresis. In the nine HCC patients, binding of 125I-insulin averaged 13% by ethanol separation and 0.018 mU/ml with radioimmunoelectrophoresis, levels that were similar to those of patients with noncancerous liver disease and significantly higher than those of the healthy controls. Mean binding of 125I-glucagon was 11% in HCC sera. Serum binding of labeled hormones correlated significantly with IgG concentrations in the patients. The second part of the study attempted to define the nature of insulin binding in HCC and other forms of liver disease. After confirmation of the increased serum binding of labeled insulin by another method of precipitation, PEG, an attempt was made to compete with the labeled insulin for its serum binding sites by adding a large amount of unlabeled insulin. This binding was not displaceable, however, and was therefore considered nonspecific. When the same procedures were repeated using normal serum to which increasing amounts of gamma globulin were added, the nonspecific binding of insulin increased in a linear fashion. Furthermore, a similar degree of high nonspecific insulin binding occurred in six patients with multiple myeloma and raised serum IgG concentrations. We therefore conclude that in the many clinical situations where hypergammaglobulinemia exists, false positive tests for the detection of antibodies against insulin (and probably other peptide hormones) will emerge unless appropriate methods are used to check for nonspecific peptide binding.
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PMID:Nonspecific blinding of insulin to gamma globulin in the serum of black patients with hepatocellular carcinoma and other forms of liver disease. 618 Jan 12

Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested in vitro and in vivo for their anti-tumor activity. They were equally cytotoxic to rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates either by intraperitoneal or intravenous injections. Daunomycin conjugates with horse anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal immunoglobulin. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls delayed only slightly tumor development.
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PMID:Chemotherapy by intravenous administration of conjugates of daunomycin with monoclonal and conventional anti-rat alpha-fetoprotein antibodies. 618 54

Monoclonal antibodies to rat alpha-fetoprotein (AFP) were produced by hybridization of mouse myeloma cells with spleen cells from mice immunized with rat AFP. The monoclonal antibodies as well as horse anti-rat AFP antibodies were coupled via a dextran bridge to daunomycin. Both types of conjugates were tested for their antitumor activity in vitro and in vivo. They were equally cytotoxic to the rat AH66 hepatoma cell line in culture. Rats challenged with hepatoma cells were treated with the conjugates by either intraperitoneal or intravenous injection. Daunomycin conjugates with horse-anti-AFP and monoclonal mouse anti-AFP were capable of delaying the tumor development more efficiently than were the controls of antibodies or free drug, mixtures of drug with antibodies, and a conjugate of drug and normal Ig. The specific conjugates were considerably more effective when the treatments were given intravenously. The specific conjugates produced 60% long-term survival, whereas the controls only slightly delayed tumor development.
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PMID:Effect of a conjugate of daunomycin and purified polyclonal or monoclonal antibodies to rat alpha-fetoprotein on the growth of alpha-fetoprotein-producing tumor cells. 620 34

Hybrid cell lines which secreted antibodies to liver-specific membrane lipoprotein (LSP) were obtained by immunizing SMA and BALB/c mice with human LSP and fusing their splenocytes with the myeloma cell line P3-NSI/1-Ag4-1. The secretion of antibody to LSP (anti-LSP) was monitored by binding to a human hepatocellular carcinoma cell line, SK-Hep-1, which possesses surface membrane LSP, and to 125I-antimouse F(ab')2 antibody in radiobinding assay, and by reacting with 125I-LSP in double-antibody radioimmunoassay. From four separate cell fusions, seven secreting hybrids were cloned by dilutional techniques. Of these, four cell lines produced antibodies reacting with a wide variety of cells. The culture supernatants of the remaining three (6D6, 6G3 and 8F10) demonstrated the strongest binding activities against SK-Hep-1 among the various kinds of cell lines tested. However, binding with other cell lines, including renal cancer cells (SK-RC-6) and myeloid cell (HL-60) also occurred. Absorption test of ascitic fluids derived from 6D6 showed that ascitic fluids lost their capacity to bind to target SK-Hep-1 cells when absorbed with SK-Hep-1. Similarly absorption by SK-RC-6 and HL-60 removed almost all of the binding activity of ascitic fluids. Moreover, the binding activities of the ascitic fluids to SK-RC-6 and HL-60 were eliminated when absorbed with SK-RC-6, HL-60 and SK-Hep-1. The present study indicates that our LSP preparation contains nonspecific organ antigens, and although LSP exists on liver cell membrane, it is also found on the cell membrane of other organs albeit in less quantity.
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PMID:The specificity of human liver membrane lipoprotein: studies with monoclonal antibodies. 620 Apr 16

BALB/c mouse splenocytes from mice immunized with cells of the human hepatoma line Hep G2 were fused with SP2/0-Ag 14 mouse myeloma cells. Two monoclonal antibodies recognizing antigenic determinants (Hag-1, Hag-2) of hepatoma cell surface molecules were investigated. Analysis of immunoprecipitates by sodium dodecyl sulfate (SDS) gel electrophoresis revealed that the Hag-1 antigenic determinant is born ona 115, kD MW glycoprotein, and that the second antibody immunoprecipitates a group of surface proteins with MW of 230 kD, 79 kD, 23 kD, and 20 kD from human hepatoma cells. These antigenic determinants are present on cell lines derived from other human tumors, thus neither of the antibodies is hepatoma-specific; cross-reactivity with human colorectal carcinoma and some mammary carcinoma cell lines is notable. Using indirect immunofluorescence on frozen sections Hag-1 was detected in one of three liver biopsies tested whereas Hag-2 was demonstrated in all three. Both antigens were detected in sections of human kidney with Hag-2 localized to the proximal tubules.
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PMID:Identification of human hepatoma-defined cell surface molecules. 620 70


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