Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In an effort to identify cellular proteins that may be involved in the Abelson murine leukemia virus (A-MuLV) transformation process, we have isolated a hybridoma antibody (6C3) that detects a tumor-associated antigen in all A-MuLV-induced pre-B-cell lymphomas. The 6C3 antibody immunoprecipitates two molecules of Mr 160,000 and Mr 125,000 from metabolically labeled A-MuLV tumors. The two proteins recognized by the 6C3 antibody are distinct from the A-MuLV-transforming protein in that they lack viral gag determinants and are neither phosphoproteins nor protein kinases. The 6C3 proteins can be detected in all A-MuLV pre-B-cell lymphomas and some nonviral B lymphomas but are not detected on any other tumor or normal cell, including A-MuLV-transformed fibroblast lines. Thus, the 6C3 proteins may represent the products of novel cellular genes whose expression is induced, stabilized, or amplified in B-cell tumors of both viral and nonviral origin. Further evidence in support of this hypothesis is provided by the finding that 6C3 antigen expression correlates with autonomous cell growth and the transformed phenotype in both normal bone marrow cultures and those infected with A-MuLV.
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PMID:Transformation-associated proteins in murine B-cell lymphomas that are distinct from Abelson virus gene products. 661 51

The induction of immune resistance to L1210 murine leukemia by 3 types of L1210 vaccines was compared under conditions in which in vitro cell proliferation and transplantability to mice were completely suppressed. L1210 cells treated with glutaraldehyde plus concanavalin A (ConA) were more potent in inducing antitumor immunity than those treated with Vibrio cholerae neuraminidase or mitomycin C (MMC). This and the finding that cell-bound ConA enhanced the immunogenic potency of MMC- or formaldehyde-treated L1210 vaccines indicate that ConA endowed the cells with additional potency in inducing antitumor immunity. ConA-free and ConA-bound vaccine cells took up the same amount of anti-L1210 antibody, suggesting that cell-bound ConA did not increase tumor-associated antigen molecules on the tumor cell surface. However, adoptively transferred spleen cells of mice sensitized with ConA-bound, but not ConA-free, vaccine amplified the vaccine-induced antitumor immunity in the recipients. These donor spleen cells suppressed the in vitro proliferation of live L1210 cells no more than non-primed spleen cells, nor was their amplifying activity abrogated by treatment with anti-Lyt-2.1 antibody and rabbit sera as a source of complement. This indicated that cytotoxic T cells and/or their precursors were not involved in the observed amplification. This as well as the finding that their amplifying activity was completely abrogated by treatment with rabbit anti-mouse brain-associated T cell antigen antisera and rabbit sera as a source of complement, led us to conclude that amplifier T cell production, associated with vaccine-bound ConA, was responsible for the enhanced immunogenic potency of ConA-bound vaccines.
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PMID:Immunogenicity and amplifier cell production by tumor vaccines enhanced by concanavalin A. 681 60

The nonimmunogenic thymic leukemia TH, obtained in mouse strain CBA/Ht, was adapted to culture. By in vitro treatment of a clonal TH cell line with the mutagen N-methyl-N'-nitro-N-nitrosoguanidine, stable variant cell clones (tum-) were obtained that elicited a rejection response in syngeneic mice. Mice that had rejected a tum- variant were partially protected against a challenge with the original tumor. When spleen cells of these animals were restimulated in vitro, cytolytic T cells were obtained that were directed against an antigen present on the original tumor. The existence of these cytolytic effectors was confirmed by clonal analysis of the cytolytic response. No immune protection against TH was observed in mice that had been immunized with irradiated cells of the original TH tumor. These results confirm that tum- variants can elicit a syngeneic rejection response against tumors that are apparently devoid of transplantation immunogenicity. The experimental conditions and the results make it likely but not certain that the tumor-associated antigen detected on leukemia TH was present on the primary tumor.
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PMID:Protection against a nonimmunogenic mouse leukemia by an immunogenic variant obtained by mutagenesis. 698 14

Carcinoembryonic antigen (CEA), a oncofetal glicoprotein, has been regarded as specific marker for colorectal cancer initially and restricted to the significance of tumor-associated antigen afterwards. Circulating CEA levels were determined in 47 patients with hematologic malignancies, resulting elevated in 10 (21%). The highest values had been discovered in a chronic lymphocitic leukemia complicated by primary hepatoma, causing the problem of the role played by the second tumor, likewise to another CEA-positive patient with the association "Hodgkin's disease-pancreatic carcinoma". The CEA employment had not been particularly satisfactory in the therapeutic monitoring and in the early detection of the relapses, in opposition to the results referred in the colorectal, mammary and bronchogenic carcinoma.
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PMID:[Evaluation of carcinoembryonic antigen (CEA) in patients with neoplasms and hematologic diseases]. 734 Jul 29

The idioptypic (Id) determinant of immunoglobulin expressed on the cell surface of malignant B cells represents a prototypical tumor-associated antigen (TAA), which has been used in a purified soluble form for active immunization in experimental tumor models and human hematological malignancies. Using a spontaneous transplantable murine model of B cell leukemia/lymphoma (BCL1), we have demonstrated the expression of the B7 costimulatory molecules in addition to the previously described Id determinant and class II major histocompatibility antigens. Intact irradiated BCL1 cells bearing these distinct determinants induced long lasting antitumor immunity in naive syngeneic mice. Induction was dose-dependent and most effective when three doses of 30 x 10(6) intact irradiated BCL1 cells were given at intervals of 7-10 days. The induced immunity protected 96% of 28 mice inoculated with a lethal dose of 10(5)-10(6) nonirradiated BCL1 cells and 85% of 27 mice given a second challenge, whereas control mice died on day 20 after inoculation with 10(6) BCL1 cells. Adoptive transfer of splenocytes derived from immune mice did not induce leukemia in syngeneic recipients. Such splenocytes, harvested more than 365 days following immunization and administered together with fresh BCL1 cells to adoptive recipients, were able to confer protection for 90 days, even following a second challenge given 104 days after the first one. BCL1 immune splenocytes transferred into BCL1-bearing mice exerted a therapeutic effect, preventing leukemia onset for at least 180 days. Our results demonstrate the ability of tumor cells to trigger effective anti-tumor immunity. These findings could ultimately be applied to the prevention of tumor relapse in treatment of hematological and other malignancies expressing TAA, class II MHC antigen and costimulatory molecules.
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PMID:Induction of tumor immunity by intact irradiated leukemic B cells (BCL1) bearing a tumor-associated cell-surface idiotype and the costimulatory B7 molecule. 748 66

Five monoclonal antibodies detected a surface antigen expressed exclusively on T-cell acute lymphoblastic leukemia (T-ALL) in a panel of 45 human hematopoietic cell lines, including T-cell lines derived from adult T-cell leukemia and those established by immortalization with human T-cell leukemia virus type 1 or Herpesvirus saimiri. Peripheral blood mononuclear cells, including fresh and activated T cells, were also completely devoid of this antigen. We designated this antigen as TALLA-1 (from T-ALL-associated antigen 1). By expression cloning, a cDNA clone encoding TALLA-1 was isolated from T-ALL cell line Molt-4. TALLA-1 was found to be a member of the transmembrane 4 superfamily (TM4SF). The cDNA was also essentially identical to A15, which was isolated from another T-ALL cell line, HPB-ALL, by differential hybridization with normal peripheral blood lymphocytes, and to CCG-B7, which was isolated from a brain cDNA library using CCG repeat as a probe. The gene product was now characterized in detail at the protein level. Northern blot analysis showed that the gene was expressed most strongly in brain, skeletal muscle and spleen. In a panel of 52 non-hematopoietic human cell lines, the majority of neuroblastoma cell lines were found to be positive for TALLA-1. Like ME491, CO-029 and L6, TALLA-1 may be another TM4SF member behaving as a potential tumor-associated antigen.
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PMID:Identification of a highly specific surface marker of T-cell acute lymphoblastic leukemia and neuroblastoma as a new member of the transmembrane 4 superfamily. 776 45

Distribution of subpopulations of lymphocytes in the lymph nodes and tumor tissues from cattle with enzootic bovine leukosis (EBL) was examined by immunohistology using a panel of monoclonal antibodies against leukocyte differentiation molecules of bovine leukocytes and tumor-associated antigen (TAA) of EBL. As disease progressed in the lymph nodes, TAA positive cells increased in number and were strongly positive. The number of B-B2, IgM positive cells were reduced in frequency in the follicle and areas of neoplastic cell-proliferation. Alpha beta and gamma delta T cells positive for WC1 (workshop cluster designation) were reduced in frequency due to infiltration and proliferation of neoplastic cells. In tumor tissues which were thought to consist with monoclonal population of cells carrying BLV provirus, strongly TAA-positive cells were present throughout the section. Most of the neoplastic cells from five cattle with EBL appeared to be divided into four types, CD2-, CD4-, CD8-, WC1-, B2+ or B2-, IgM+ or IgM-, MHC II+ and strong TAA+. WC1+ cells played no apparent role in the development of lymphosarcoma of EBL. WC1+ cells were not observed in tumor tissues. However, the possibility of effect of T cell for tumor immunity was suggested, since TH/l and Tc/s cells were scattered in the tumor tissues.
Leukemia 1994 Apr
PMID:Phenotype analysis of lymphocytes present in different stages of neoplasia induced by bovine leukemia virus. 815 94

By using the monoclonal antibody (MAb) c143 against tumor-associated antigen that is expressed in tumor cells of cattle with bovine leukemia virus (BLV)-induced enzootic bovine leukosis (EBL), we found a novel bovine MHC class II-related antigen which consists of alpha chain (36-37 kDa) and beta chain (32 and 34 kDa). The nature of the c143 antigen was different from previously identified class II antigens, such as DR and DQ, as indicated by test for reactivities with mouse L cell transfectants expressing human class II antigens, sequential immunoprecipitation and tryptic peptide mapping. With the progression of EBL, the number of cells carrying the c143 antigen increased, and the beta chain was specifically phosphorylated at serine residue(s) in lymphosarcoma cells and the cell lines derived from them. A marked difference between expression patterns of the c143 antigen and the class II antigens was observed in lymph nodes from BLV-free and -infected animals. Although bovine mixed lymphocyte reaction (MLR) was inhibited by the addition of MAbs against class II antigens, the c143 MAb did not inhibit a lymphoproliferative response of T cells in the MLR, suggesting that the function of this antigen is distinct from those of classical class II molecules. Significantly, although the human homologue of the c143 antigen is expressed little if at all in human T-cell lines, such as CEM, Molt-4, Jurkat and HPB-ALL, its expression become apparent in T-cell lines infected with human T-cell lymphotrophic virus I (HTLV-1).
Leukemia 1994 Apr
PMID:Identification of tumor-associated antigen that is expressed on bovine leukemia virus-induced lymphosarcoma cells and expression of its human homologue in human T-cell lymphotrophic virus I-infected cell lines. 815 99

Immunization of mice with Moloney murine leukemia virus (MoMuLV) induces the generation of a population of CTL which recognizes a non-viral, tumor-associated antigen (TAA) expressed on MuLV-induced tumors. To determine whether this TAA could be used as a pre-leukemic or leukemic cell marker, CTL clones directed against Moloney viral and TAA antigen were used to analyze viral and TAA antigen expression on chronically infected and leukemic lymphoid cells obtained from mice inoculated neonatally with MoMuLV. Although both sets of cells could be recognized and lysed by viral antigen specific CTL, they are not recognized by TAA-specific CTL. Only after transformed cell lines were established from leukemic spleen cells could susceptibility to TAA-specific CTL be observed. Thus, the appearance of the MoMuLV-TAA was restricted to MoMuLV-transformed cells.
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PMID:Expression of the MuLV-tumor-associated antigen is restricted to MuLV-transformed cells. 838 66

Radiolabeled monoclonal antibodies have been used for radioimmunotherapy studies with human tumor spheroids and murine and human tumor xenografts in experimental animals. This paper reviews the work that has been performed in these models with different types of cancer, and highlights those papers that have presented dosimetry estimates and attempts to correlate the findings. Radioimmunotherapy studies in multicell spheroids, as a model for micrometastases, have been performed in human neuroblastoma, colon cancer, and melanoma cell lines using 131I-, 125I-, 186Re-, and 212Bi-labeled antibodies. The uniform geometry of the spheroid has allowed radiation dose estimates to be made. Up to three logs of cell kill have been achieved with 131I- and 186Re-specific antibody with minimal toxicity from labeled nonspecific antibody, but 212Bi-antibody had little effect because of its short half-life as shown by Langmuir. It appears that the two most important factors for therapeutic efficacy in this model are good penetration of the radiolabeled antibody and an adequate radionuclide half-life to allow penetration of the immunoconjugate prior to significant radionuclide decay. Radioimmunotherapy studies in animals bearing transplants of colon cancer, leukemia, lymphoma, hepatoma, renal cell carcinoma, neuroblastoma, glioma, mammary carcinoma, small cell lung carcinoma, cervical carcinoma, ovarian carcinoma, and bladder cancer have been performed with 131I, 90Y, 186Re, 153Sm, and 177Lu beta emitting, and 212Bi alpha emitting radionuclides conjugated to monoclonal antibodies. A few studies compared different radionuclides in the same model system. The approaches that have been used in these studies to estimate tumor dosimetry include the MIRD approach, thermoluminescent dosimetry, autoradiography, and comparison to external irradiation. The majority of investigators have estimated the dose to tumor and normal organs using MIRD-based calculations (time-activity curve and equilibrium dose constant method). The range of tumor doses has been between 17 and 11 171 mGy/MBq of administered radioactivity. The effectiveness of radiolabeled monoclonal antibody therapy depends on a number of factors relating to the antibody such as specificity, affinity, and immunoreactivity. The density, location, and heterogeneity of expression of tumor-associated antigen within tumors will affect the localization and therapeutic efficacy of radiolabeled antibodies, as will physiological factors such as the tumor vascularity, blood flow, and permeability. These factors are discussed and examples are presented.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Experimental radioimmunotherapy. 849 64


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