Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The beta-subunit gene of TSH is specifically expressed in thyrotrope cells of the anterior pituitary gland. To define the particular TSH beta-subunit gene sequences responsible for tissue-specific expression, TSH beta promoter fragments were assessed for promoter activity by gene transfer into TSH-expressing thyrotropic tumor cells (TtT-97). Previous studies have shown that the murine TSH beta gene promoter was more efficiently used in TtT-97 cells compared to other pituitary-derived cells or nonpituitary fibroblasts and that a 191-basepair DNA sequence of the 5' flanking region between -271 and -80 was sufficient for maximal promoter activity in thyrotropes. Further deletional analysis within this region has localized the area responsible for expression in thyrotropes to a 37-basepair region between -117 and -80 up-stream of the major transcriptional initiation site. DNase-I protection assays demonstrated that this functionally defined 5' flanking area, in addition to the adjacent sequences immediately up-stream and down-stream, interacts with protein factors present in nuclear extracts from TtT-97 tumor cells. When fused to a heterologous promoter, fragments derived from the region between -271 and -80 exhibited cell-specific activity, although this was not conferred solely by the TSH beta promoter fragment from -117 to -80. Heterologous promoter activity was further stimulated when fragments containing the areas from -271 or -201 to -77 were used, suggesting combinatorial cis interactions between these regions of the TSH beta promoter. DNase-I protection studies suggest that there are multiple protein-binding domains in the mouse TSH beta 5' flanking sequence. Only the more proximal domains, which encompass important promoter elements, appear to be required for efficient expression in thyrotropes, whereas other more up-stream sites of protein interaction may be involved in regulatory aspects of TSH beta gene expression.
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PMID:Protein factors in thyrotropic tumor nuclear extracts bind to a region of the mouse thyrotropin beta-subunit promoter essential for expression in thyrotropes. 208 88

Benign cementoblastoma is a rare odontogenic tumour localized in the jaws of young people. Benign cementoblastoma has characteristic radiologic and microscopic features and it appears to be fused to the tooth roots. The most important differential diagnosis is-with a benign osteoblastoma. The tumor should be enucleated and the teeth extracted. This case represents only the third reported case of a benign cementoblastoma associated with a third molar.
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PMID:Benign cementoblastoma: review of the literature and report of a case at an unusual location. 210 57

Human lymph node lymphocytes from cancer patients were fused with either the UC 729-6 or SHFP-1 human fusion partners. Resulting human-human hybridomas were tetraploid, expressed markers from both parent cells, and secreted approximately 1 microgram Ig/10(6) cells/ml/day. Immunofluorescence analysis of some of the human MAbs with a panel of normal and malignant cell lines revealed a staining pattern of only the nuclear region. One IgM secreting hybridoma, TLN1F4, derived from a teratocarcinoma lymph node, predominantly stained the nuclear regions of adherent tumor cell lines and no hematopoietic cell lines or normal fibroblasts. PLN3C8, an IgG1 secreting hybridoma, derived from a prostate carcinoma lymph node, predominantly stained the nucleolus of LnCap, a a carcinoma of the prostate cell line. CLN2E5, an IgM secreting human hybridoma, derived from a carcinoma of the cervix lymph node, predominantly stained both cytoplasmic and nuclear components to tumor cell lines and not normal fibroblasts or hematopoietic cell lines. These data suggest that the immune response occurring within regional draining lymph nodes is capable of recognizing nuclear-associated antigens.
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PMID:Human monoclonal antibodies to nuclear antigens. 210 55

Human-human hybridomas were generated using pokeweed mitogen-stimulated lymphocytes from the regional lymph nodes of cancer patients by fusion to the LICR-2 human myeloma cell line. A total of 35 fusions, using the regional lymph node lymphocytes of cancer patients, resulted in hybrid growth in 23% of wells plated with 21 IgG ELISA positive clones, 6 of which have maintained stable human monoclonal antibody production. Mononuclear cells were separated on Ficoll-Paque and grown for 3-4 days in 1% pokeweed mitogen and fused to the LICR-2 human myeloma cell line. Human-human hybridoma producing membrane reactive IgG antibodies have been isolated and react to the following cancers: breast; melanoma. Twenty-seven fusions from 8 breast carcinoma patients resulted in 13 ELISA positive IgGs, 3 of which were stable after cloning. A total of 5,071 wells were plated after polyethylene glycol fusion with resultant hybrid growth in 1210 wells (24% hybrid growth) after hypoxanthine-aminopterin-thymidine selection. In 8 fusions using regional lymph node lymphocytes of other types of cancer, including 6 fusions using lymphocytes from malignant melanoma patients, there were 1,580 wells plated with positive growth in 20% of the wells (311 wells). Of these, 8 clones were ELISA positive and 3 stable clones all producing IgG anti-melanoma antibody were isolated. The overall hybrid frequency was 43 x 10(-7) fused lymphocytes (39 x 10(-7) non-breast and 45 x 10(-7) breast). A total of 21 IgG-producing clones were identified to crude membranes of allogeneic tumor cell lines and stable antibody production was achieved for 6 (29% stable clones).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Pokeweed mitogen-stimulated human lymphocytes fused to LICR-2 (HMY2) generate human-human hybridomas producing monoclonal IgG antibodies reactive to human breast carcinoma and malignant melanoma. 210 59

We used a recombinant retrovirus to study cell lineage in the chicken optic tectum. The virus inserts the Escherichia coli lacZ (beta-galactosidase) gene into the genome of an infected cell; a histochemical stain marks the progeny of infected cells with a blue precipitate. We had previously shown that individual clones frequently contain diverse neuronal types. Now we asked whether individual clones contain glia as well as neurons. To this end, we constructed a virus in which lacZ is fused to a nuclear localization signal sequence from the simian virus 40 large tumor antigen. Cells infected with this virus are marked with blue nuclei instead of blue somata. In embryos injected with a mixture of the two retroviruses, individual clusters contained cells with only one label type (nuclear or cytoplasmic), thus verifying that clusters of cells were clones. Furthermore, it was possible to immunostain the somata of cells that had blue nuclei, whereas the blue cytoplasmic precipitate hampered immunostaining. Together, these methods allowed us to show that some clones contained neurons (neurofilament-positive) and two types of glia (glutamine synthetase-positive and glial fibrillary acidic protein-positive). This result demonstrates the existence of a common progenitor for neurons and glia in optic tectum.
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PMID:Neurons and glia arise from a common progenitor in chicken optic tectum: demonstration with two retroviruses and cell type-specific antibodies. 210 84

To be capable of selective killing of tumor cells, the non-selective Pseudomonas aeruginosa exotoxin A must have its cell-binding domain inactivated or removed and then be chemically linked to, or genetically fused with, a specific targeting agent. In the present study, epsilon-NH2 groups of lysine residues of the cell-binding domain of exotoxin A were extensively propionylated with N-succinimidyl-3-propionate (NSP). The NSP-treated exotoxin retained its cytocidal ADP-ribosyltransferase activity, but it could no longer bind to, and inhibit the proliferation of, Friend murine erythroleukemia cells. Cytotoxicity (i.e., the ability to inhibit proliferation) for the Friend erythroid cells was restored completely to the NSP-inactivated exotoxin by conjugating it to ADIF, an autocrine factor secreted by chicken erythroleukemia cells which selectively inhibits the differentiation of erythroid cells such as Friend erythroleukemia cells without inhibiting their proliferation.
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PMID:The cytotoxicity of Pseudomonas exotoxin A, inactivated by modification of the cell-binding domain I, is restored when conjugated to an erythroid cell-specific targeting agent. 210 50

The chimeric toxin IL6-PE40, which is composed of interleukin 6 (IL6) fused to a mutant form of Pseudomonas exotoxin (PE) devoid of its native cell recognition domain, can kill myeloma and hepatoma cells which express high levels of IL6 receptors. To enhance the usefulness of IL6-PE40 on potential target cells, we have attempted to develop more potent IL6-PE derivatives. We have developed nine new IL6-PE derivatives and assessed their cytotoxicity on human myeloma cells. Two of these new forms, IL6-domain II-PE40 and IL6-PE664Glu were more toxic to myeloma cells bearing IL6 receptors than was IL6-PE40. These two chimeric toxins were compared with IL6-PE40 for cytotoxicity toward a variety of tumor cell lines. We found that most tumor cell lines which are sensitive to IL6-PE40 are more sensitive to IL6-domain II-PE40 and IL6-PE664Glu. Cells with as few as 200-600 IL6 receptors/cell could be killed. The specificity of these chimeric toxins was shown through competition with recombinant IL6. Toxicity studies in mice demonstrated that the two new molecules had an LD50 of 10-20 micrograms/mouse. This compares to an IL6-PE40 LD50 of 20 micrograms/mouse. The new IL6-toxins could be detected in the serum up to 8 h after intraperitoneal administration with a peak at 1 h. These data suggest that IL6-domain II-PE40 and IL6-PE664Glu may be more useful than IL6-PE40 in killing IL6 receptor-bearing tumor cells in animals.
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PMID:Cytotoxicity of IL6-PE40 and derivatives on tumor cells expressing a range of interleukin 6 receptor levels. 211 4

Novel islet cell, duct cell, and acinar cell markers have been identified by monoclonal autoantibodies (Maab) derived from prediabetic BB rats. Spleen cells from two rats that both developed diabetes after splenectomy were fused with mouse myeloma cells. A cellular immunoradiometric assay for differential reactivity toward the surface of two closely related, insulin- and non-insulin-producing rat islet tumor cell lines was used to select and clone several IgM-producing hybridomas. The supernatants were finally characterized by two-color immunofluorescence with islet hormone antisera on frozen sections of human, monkey, and rat pancreas. Maab EB52 stained PP cells, but also few A cells on rat pancreas. Maab CA812 identified a subpopulation of islet D cells on rat, human and monkey pancreas. Although the CA812-reactive antigen and somatostatin were coexpressed in most D cells in adult rat pancreas, only a few islet D cells were stained in the newborn pancreas. The CA812-reactive antigen was not detected in somatostatin-producing cells in the duct epithelium. Maab H37 and IF5 selectively stained acinar cells in rat, human, and monkey pancreas, whereas Maab DA39 identified the rat ductal epithelium including the scattered endocrine cells of the ducts. In summary, B lymphocytes producing autoantibodies to pancreatic endocrine, exocrine, and ductal markers are present in prediabetic BB rats and can be detected by use of transformed pluripotent islet cells as target. Such B lymphocytes can be immortalized to produce monoclonal antibodies to study their role in insulin-dependent diabetes mellitus pathogenesis and to clarify the development of the pancreas.
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PMID:Novel islet, duct, and acinar cell markers defined by monoclonal autoantibodies from prediabetic BB rats. 212 46

We used somatic cell hybridization to determine whether the regressor phenotype exhibited by UV-induced murine tumors was dominant or recessive and whether this technique could confer immunogenic properties on nonimmunogenic syngeneic tumors. We transfected a highly antigenic UV-induced C3H mouse tumor cell line (UV-2240) with the plasmid pSV2-neo and selected G418-resistant clones. The resulting cell line was fused with a spontaneously transformed nonimmunogenic C3H progressor tumor cell line (SF-2T) that had been selected previously for resistance to 3.0 mM ouabain. These two cell lines were fused by a brief exposure to polyethylene glycol and heterokaryons isolated by growth in medium containing both G418 and ouabain. Hybrid cell lines established from individual colonies and from pools of colonies were tested for tumorigenicity in normal C3H and athymic nude mice. The results indicated that all the hybrid cell lines tested were highly antigenic in that they were completely rejected when transplanted into normal syngeneic mice but grew progressively in nude mice. Furthermore, immunization of C3H mice with the hybrid cell lines induced protective immunity against challenge with the immunizing tumor and generated cross-protective immunity against challenge with the regressor parental cell line but not against challenge with the progressor parental cell line. These results demonstrate that the regressor phenotype of the UV-2240 tumor is dominant in nature and that the immune response induced by somatic cell hybrids is uniquely directed against the dominant tumor-specific transplantation antigens expressed on the regressor tumor. This implies that introduction of tumor-specific transplantation antigens from an immunogenic tumor into a nonimmunogenic tumor, although sufficient to confer immunogenic properties to the hybrid, is insufficient to induce cross-protective transplantation immunity against the nonimmunogenic tumor.
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PMID:Immune response to somatic cell hybrids between ultraviolet radiation-induced regressor and spontaneous progressor C3H mouse tumor cells. 213 70

Murine monoclonal antibody therapy of human cancer rarely induces clinical responses. Antibody-induced cellular infiltrates rarely accumulate at sites of tumor, even in clinically responding lesions. Thus, the ability of these antibodies to promote host effector cell-mediated lysis of tumor via antibody-dependent cellular cytotoxicity (ADCC) has not been harnessed by existing treatment approaches. One potential explanation is that ADCC requires binding of antibody Fc domains to cellular Fc gamma receptors, and therapeutically administered murine antibodies must compete with vast excesses of human IgG for Fc gamma receptor occupancy. Chemically linked antibody heteroconjugates that bind selected target and effector cell structures via distinct Fab portions can mediate lysis of malignant cells in vitro in the presence of human serum. This approach addresses a potentially major obstacle to antibody therapy. Production of bispecific monoclonal antibodies with similar specificities and superior in vivo biodistribution characteristics would thus have potential clinical applications. We have prepared and purified a bispecific, monovalent monoclonal antibody and evaluated its in vitro effects. The IgG1-secreting hybridoma line 3G8 (alpha-human Fc gamma R III) was fused with the hybridoma line CA19-9, which produces an IgG1 antibody that binds to a glycoprotein shed by gastrointestinal cancers. Multiple clones with bispecific binding properties were identified. CA19-9 x 3G8 clonal supernatants and purified antibody, but not the parent antibodies, efficiently mediated specific in vitro lysis of cells of the SW948 line by human large granular lymphocytes (LGLs). Human serum-resistant target cell lysis augmentation at low effector:target ratios was seen using picogram amounts of antibody. In contrast, the IgG2 alpha variant of CA19-9, which also promotes ADCC by LGLs, was unable to augment lysis of SW948 cells when effectors were preincubated with human serum. This bispecific, monovalent monoclonal antibody is an efficient promoter of the anti-tumor effects of LGLs in physiological concentrations of human serum. In vivo models that evaluate treatment efficacy and promotion of inflammatory tumor infiltrates by bispecific monoclonal antibodies are required to assess the therapeutic potential of these novel constructs.
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PMID:Potentiation of tumor lysis by a bispecific antibody that binds to CA19-9 antigen and the Fc gamma receptor expressed by human large granular lymphocytes. 214 12


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