Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: 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)

Human and mouse lymphocytes were surface-labeled by lactoperoxidase-catalyzed iodination, or by galactose oxidase oxidation followed by reduction with tritiated sodium borohydride. The labeled cells were lysed with Nonidet P-40. Proteins binding to Helix pomatia A hemagglutinin (HP) were isolated by affinity chromatography on HP-Sepharose and analyzed by sodium dodecyl sulfate polyacrylamide gel electrophoresis and autoradiography. A major cell surface glycoprotein (apparent mol. wt. 150 000, using reducing conditions) on human lymphocytes was responsible for almost all binding of HP. This protein was present on normal and malignant thymus-derived lymphocytes, e.g. thymocytes, blood T cells and T leukemia cell lines. It was also found on chronic lymphocytic leukemia cells, one null cell leukemia line, one unidentified leukemia line, one lymphoblastoid cell line of B origin and on one stem cell lymphoma line. In contrast, this protein was not found on various B cells at different steps of differentiation, e.g. four B lymphoma lines or one myeloma line. It was also absent from a histiocytic leukemia line. However, two of the four B lymphoma lines and the myeloma line had another HP-binding surface glycoprotein (mol. wt. 200 000) instead of the 150 000 protein. Studies of mouse lymphocytes similarly showed that thymus-derived lymphocytes (normal and malignant) but not normal adult B cells expressed a major HP-binding surface glycoprotein of apparent mol. wt. 130 000 (reducing conditions).
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PMID:Helix pomatia A hemagglutinin: selectivity of binding to lymphocyte surface glycoproteins on T cells and certain B cells. 30 19

BCA200 has been described as a 200,000 Mr monomeric cell surface glycoprotein associated with human breast cancer. Since the physical properties and cellular distribution of BCA200 resemble those of c-erbB-2, antibodies to BCA200 were tested for the ability to bind a recombinant protein containing the c-erbB-2 extracellular domain (erbB-2 ECD). Three antibodies to distinct epitopes of BCA200 reacted with erbB-2 ECD but not with a control protein expressed in a similar baculovirus lysate. Control myeloma proteins and antibodies to four other antigens did not react with erbB-2 ECD. A protein with the expected molecular weight for erbB-2 ECD was also immunoprecipitated by anti-BCA200 antibody 520C9. We conclude that BCA200 is another synonym for c-erbB-2.
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PMID:Identity of BCA200 and c-erbB-2 indicated by reactivity of monoclonal antibodies with recombinant c-erbB-2. 171 33

CD4 is a cell surface glycoprotein that identifies the subset of human T lymphocytes that induces sIg+ B lymphocytes to differentiate and secrete Ig after intimate T-B cell contact. In the course of studying a recombinant, truncated form of CD4 (rT4) we noticed that goat antibodies of apparently irrelevant specificities bound to immobilized rT4. To directly study whether rT4 interacts with Ig molecules, purified human IgG was added to rT4-coated wells and a dose-dependent interaction between IgG and rT4 was observed by ELISA. Purified myeloma IgG proteins bound to immobilized rT4 with the same avidity as polyclonal IgG that suggests that rT4-IgG binding was not due to the presence of anti-rT4 antibodies in the IgG fraction. IgG from 6 sera bound to rT4 in concentration dependent manner similar to purified IgG. Immobilized rT4 specifically bound IgG, and not IgM, IgA, IgD, or beta 2-microglobulin. The specific interaction of rT4 and IgG was also observed when IgG or IgM were immobilized, demonstrating that IgG binding was not a unique property of immobilized rT4. As with low affinity receptors for IgG, rT4 bound heat aggregated IgG with increased avidity. Neither anti-CD4 mAb nor dextran sulfate inhibited rT4-IgG binding. rT4 bound Fc but not F(ab)2 fragments. Each of the purified IgG subclasses; IgG1, 2, 3, and 4 bound to rT4 with similar avidity. Taken together, these data suggest that rT4 specifically interacts with a public structure on IgG Fc.
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PMID:Recombinant, truncated CD4 molecule (rT4) binds IgG. 229 93

Two human tumor cell lines exhibiting acquired multidrug resistance (MDR) with increased expression of a cell surface glycoprotein (GP-170) were tested for their sensitivity to human recombinant tumor necrosis factor (rTNF). The drug resistant mutant lines (CEM/V, a T-cell leukemia line resistant to vinblastine, and 8226/D, a multiple myeloma line resistant to doxorubicin), were markedly more sensitive to rTNF in clonogenic assay than were their drug-sensitive parental lines (CEM, 8226). As determined by radioreceptor assay, the number of cell surface receptors for rTNF did not differ on the parental and drug-resistant lines. During the first 24 hours after addition of rTNF, there was a decrease in intracellular ATP content in the CEM/V line but not in the CEM line. No differential effect of rTNF on ATP content was observed between 8226 and 8226/D. As determined by RNA dot-blot analysis, total cellular RNA for GP-170 was increased in the 8226/D cells. After rTNF exposure, expression of total cellular RNA for GP-170 was not altered. Accumulation of radiolabeled doxorubicin by 8226/D cells was not altered by previous or coincubation with rTNF. These findings suggest that the effects of rTNF on MDR cells is not related to TNF receptor number and is mediated at a step subsequent to rTNF binding and not by either inhibition of synthesis of GP-170 or by alteration in the function of the GP-170 efflux pump.
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PMID:Effects of tumor necrosis factor on sensitive and multidrug resistant human leukemia and myeloma cell lines. 279 Jan 97

A monoclonal antibody, NDS 58, was produced by fusing the rat myeloma line Y3 Ag 1.2.3 with spleen cells from AS rats immunized with LEW thymocytes. The determinant recognized by this antibody is leucocyte-specific and present on all thymocytes, lymph node lymphocytes and some bone marrow cells. The strain distribution of NDS 58 was consistent with it being directed at the RT7a allele. Biochemical studies established that this antigen was carried on a cell surface glycoprotein with an apparent molecular weight on thymocytes of 190,000. This study confirms that the alloantigen originally designated Ly-1, and now termed RT7, is an allodeterminant of the LC molecule, and the controversy in this area, particularly with regard to the ART-1 alloantigen, is discussed.
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PMID:A monoclonal alloantibody detecting a polymorphism of the rat leucocyte common (LC) antigen. 294 9

Monoclonal antibodies were raised against a cell surface glycoprotein (46K antigen) expressed by a Moloney sarcoma virus (Mo-MSV)-transformed STU mouse cell line (Sac). Although non-productively transformed Sac cells expressed the 46K antigen at their surface, transplantation of Sac non-producer cells into immunocompetent mice failed to induce anti-46K antibody production. Only transplantation of helper virus-superinfected Sac cells led to the development of anti-46K antibodies in addition to antibodies against helper virus structural antigens. Hybridomas producing anti-46K antibodies were established by fusion of mouse myeloma cells with spleen cells taken from mice bearing Sac tumour cells infected with Moloney helper virus. The monoclonal antibodies were subsequently tested against STU mouse transformants [spontaneously transformed or experimentally transformed with the progressor strain of Mo-MSV and the chemical carcinogen 3-methylcholanthrene (MCA), respectively] and BALB/c mouse transformants [transformed with Mo-MSV, simian virus 40 (SV40) or MCA]. Only one of the transformed cell lines tested, a non-producer transformant (PV-TC-77) induced with the progressor strain of Mo-MSV in an STU mouse was found to express a 46K antigen on the cell surface. The 46K surface antigen expressed by PV-TC-77 cells exhibited the same serological, biochemical and biological properties as the 46K Sac cell surface antigen. Though detectable on the surface of PV-TC-77 non-producer cells, immunocompetent syngeneic recipients of non-producer PV-TC-77 cells remained unresponsive against their 46K surface antigen. Only transplantation of helper virus-infected PV-TC-77 producer cells led to antibody development against the 46K surface antigen.
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PMID:Monoclonal antibody detects a common surface antigen on two independently established murine Moloney sarcoma virus non-producer transformants. 299 78

Monoclonal antibodies were used to study p97, a human melanoma-associated antigen (MAA). Four hybridomas, designated 4.1, 96.5, 118.1, and 8.2, were obtained by fusing mouse myeloma cells with spleen cells from mice immunized with human melanoma cells. Antibodies 4.1 and 8.2 were IgG1; antibodies 96.5 and 118.1 were IgG2a. Sequential immunoprecipitation (IP) and sodium-dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) showed that all 4 antibodies recognized the same 97 kilodalton (kD) protein. Binding studies with 125I-labeled antibody showed that antibodies 4.1 and 96.5 bound the same epitope, p97a. Antibodies 118.1 and 8.2 defined epitopes p97b and p97c, respectively. Six monoclonal antibodies (M17, L1, L10, R10, I12, and K5) specific for gp95, a kD melanoma cell surface glycoprotein were also tested. Sequential IP showed that these antibodies bound p97; p97 and gp95 are thus identical. Binding studies showed that antibody m17 bound epitope p971, and antibodies L1, L10, and R19 bound epitope p97c. Antibodies I12 and K5 defined 2 other epitopes, p97d and p97e, respectively. SDS-PAGE under nonreducing conditions indicated that p97 is monomeric, probably with intrachain disulfide bonds. Cell-surface labeling of sialic acid residues and neuraminidase digestion showed that p97 is a sialoglycoprotein. Digestion of p97 with papain or trypsin produced a stable 40 kD fragment, which expressed epitopes p971, p97b, and p97c, but not p97d or p97e.
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PMID:Structural characterization of human melanoma-associated antigen p97 with monoclonal antibodies. 616 74

Murine monoclonal antibody (mAb) 7C11 binds to the same cell surface epitope as anti-APO-1 and anti-Fas and reacts specifically with cells transfected with a cDNA encoding the human Fas antigen. Furthermore, incubation with 7C11 causes death of hematopoietic cell lines that express APO-1/Fas but not APO-1/Fas-negative cell lines. 7C11 therefore recognizes the human APO-1/Fas (CD95) antigen, a 40 to 50 kDa cell surface glycoprotein that can trigger apoptosis or programmed cell death. Expression of APO-1/Fas antigen by normal and neoplastic hematopoietic cells was determined by flow cytometry using 7C11. APO-1/Fas is expressed by approximately 30 to 40% of resting peripheral blood T cells, B cells, and monocytes and by approximately 5% of resting NK cells and thymocytes. It was not detected on granulocytes, erythrocytes, or platelets. Approximately 80 to 90% of activated T cells, B cells, and thymocytes express APO-1/Fas, as do the majority of activated NK cells. Perturbation of APO-1/Fas by 7C11 does not affect the viability of resting lymphocytes or monocytes. In contrast, activated T cells and NK cells undergo apoptosis within 3 hours of exposure to 7C11. Other mAb that stimulate T cells or NK cells do not cause rapid induction of programmed cell death. APO-1/Fas antigen is expressed by many cell lines of lymphoid and myeloid lineage. However, this antigen was detected on neoplastic cells from only one of 69 patients with acute myeloid leukemia, acute lymphoblastic leukemia, chronic myelogenous leukemia, chronic lymphocytic leukemia, or multiple myeloma. Only 3 out of 25 tumor samples from patients with non-Hodgkin's lymphoma were found to express APO-1/Fas. All three of these lymphomas harbored the bcl-2-Ig fusion gene associated with the chromosomal translocation t (14;18). Conversely, only 27% of lymphomas that possessed the bcl-2-Ig gene were found to express the APO-1/Fas antigen. Like normal activated lymphocytes, leukemia and lymphoma cells that expressed APO-1/Fas antigen were found to undergo apoptosis in vitro after incubation with 7C11. The APO-1/Fas antigen appears to regulate the growth of normal hematopoietic cells, and the marked upregulation of this antigen on activated normal lymphocytes contrasts sharply with the absence of APO-1/Fas on neoplastic cells of hematopoietic lineage. Defects in the apoptotic signal delivered through this antigen might contribute to the pathogenesis of hematopoietic neoplasms. Thus, the gene encoding APO-1/Fas can be considered a novel type of tumor suppressor gene, just as bcl-2 can be considered a cellular proto-oncogene.
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PMID:Functional consequences of APO-1/Fas (CD95) antigen expression by normal and neoplastic hematopoietic cells. 753 60

Monoclonal antibody (mAb) therapy for multiple myeloma, a malignancy of plasma cells, has not been clinically efficacious in part due to a lack of appropriate targets. We recently reported that the cell surface glycoprotein CS1 (CD2 subset 1, CRACC, SLAMF7, CD319) was highly and universally expressed on myeloma cells while having restricted expression in normal tissues. Elotuzumab (formerly known as HuLuc63), a humanized mAb targeting CS1, is currently in a phase I clinical trial in relapsed/refractory myeloma. In this report we investigated whether the activity of elotuzumab could be enhanced by bortezomib, a reversible proteasome inhibitor with significant activity in myeloma. We first showed that elotuzumab could induce patient-derived myeloma cell killing within the bone marrow microenvironment using a SCID-hu mouse model. We next showed that CS1 gene and cell surface protein expression persisted on myeloma patient-derived plasma cells collected after bortezomib administration. In vitro bortezomib pretreatment of myeloma targets significantly enhanced elotuzumab-mediated antibody-dependent cell-mediated cytotoxicity, both for OPM2 myeloma cells using natural killer or peripheral blood mononuclear cells from healthy donors and for primary myeloma cells using autologous natural killer effector cells. In an OPM2 myeloma xenograft model, elotuzumab in combination with bortezomib exhibited significantly enhanced in vivo antitumor activity. These findings provide the rationale for a clinical trial combining elotuzumab and bortezomib, which will test the hypothesis that combining both drugs would result in enhanced immune lysis of myeloma by elotuzumab and direct targeting of myeloma by bortezomib.
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PMID:Combinatorial efficacy of anti-CS1 monoclonal antibody elotuzumab (HuLuc63) and bortezomib against multiple myeloma. 1972 91

Ranpirnase (Rap), an amphibian RNase, has been extensively studied both preclinically and clinically as an antitumor agent. Rap can be administered repeatedly to patients without any untoward immune response, with reversible renal toxicity reported to be dose limiting. To enhance its potency and targeted tumor therapy, we describe the generation of a novel IgG-based immunotoxin, designated 2L-Rap(Q)-hRS7, comprising Rap(Q), a mutant Rap with the putative N-glycosylation site removed, and hRS7, an internalizing, humanized antibody against Trop-2, a cell surface glycoprotein overexpressed in variety of epithelial cancers. The immunotoxin was generated recombinantly by fusing Rap(Q) to each of the two hRS7 light (L) chains at the NH(2) terminus, produced in stably transfected myeloma cells, purified by Protein A, and evaluated by a panel of in vitro studies. The results, including size-exclusion high-performance liquid chromatography, SDS-PAGE, flow cytometry, RNase activity, internalization, cell viability, and colony formation, showed its purity, molecular integrity, comparable affinity to hRS7 for binding to several Trop-2-expressing cell lines of different cancer types, and potency to inhibit growth of these cell lines at nanomolar concentrations. In addition, 2L-Rap(Q)-hRS7 suppressed tumor growth in a prophylactic model of nude mice bearing Calu-3 human non-small cell lung cancer xenografts, with an increase in the median survival time from 55 to 96 days (P < 0.01). These results warrant further development of 2L-Rap(Q)-hRS7 as a potential therapeutic for various Trop-2-expressing cancers, such as cervical, breast, colon, pancreatic, ovarian, and prostate cancers.
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PMID:Ranpirnase (frog RNase) targeted with a humanized, internalizing, anti-Trop-2 antibody has potent cytotoxicity against diverse epithelial cancer cells. 2066 28


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