Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.23 (beta-galactosidase)
 14,648 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recognition of the carbohydrate part of cellular glycoconjugates by cell-surface sugar receptors may contribute to interactions, essential to the establishment of metastases. Comparison of the properties of strongly metastatic variants to their related, less metastatic counterparts offers a generally accepted approach to the discovery of metastasis-associated characteristics. The chemically induced murine lymphoma line Eb and its spontaneously arising variant ESb with increased potential for lung and liver colonization, the virally induced lymphosarcoma cell line RAW117-P and its in vivo selected variant H10 with increased potential for liver colonization, and the B16-F1 melanoma line and its in vivo selected variant F10 with increased potential for lung colonization, were chosen. A panel of 12 types of chemically glycosylated E. coli beta-galactosidase, exposing the pivotal carbohydrate residues for specific carbohydrate-dependent cell binding, was employed to study the expression of respective cell-surface sugar receptors on these cell lines. Specific binding occurred in a non-uniform manner for the individual probes. Systematic measurements at a non-saturating ligand concentration revealed quantitative differences between the 2 cell lines of each system. However, there were no consistent changes associated with the metastatic phenotype. A similar result was obtained employing Scatchard analyses for quantitative evaluation of binding characteristics in several cases. Surface receptor expression was responsive to chemical induction of differentiation in the lymphosarcoma model. Analyses of sugar-inhibitable cell adhesion to neoglycoprotein-coated plastic wells for the lymphoma and lymphosarcoma cells revealed that the presence of cell-surface sugar receptors, even at similar densities to those defined by neoglycoenzyme binding, will not necessarily translate into an identical adhesive response. Several carbohydrates, especially N-acetyl-D-galactosamine, can differentially affect this interaction at a non-toxic concentration in both model systems.
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PMID:Analysis of cell-surface sugar receptor expression by neoglycoenzyme binding and adhesion to plastic-immobilized neoglycoproteins for related weakly and strongly metastatic cell lines of murine tumor model systems. 216 45

The efficacy of a recombinant vaccinia virus (rvv-mGM-CSF) expressing murine granulocyte-macrophage colony stimulating factor (GM-CSF) for use in cancer gene therapy was evaluated. C57BL/6 mice with established B16-F10 melanoma were treated by s.c. injection of irradiated B16 cells infected with two different recombinant vaccinia virus (rvv) constructs. Mice treated with rvv-mGM-CSF vaccine survived longer (p < 0.05), were free of palpable tumors (> 4 mm) longer (p < 0.02), and had smaller mean tumor volumes (p < 0.005) compared to those treated with irradiated B16 cells infected with a control rvv (rvv-lacZ) expressing Escherichia coli beta-galactosidase or irradiated uninfected B16 cells. The vaccine appeared to be B16 tumor cell specific, because there was no therapeutic effect when heterologous but syngeneic (H-2b) colon adenocarcinoma cells, MC-38 infected with rvv-mGM-CSF were used as vaccine. In this model, rvv expressing interleukin-2 (IL-2) was ineffective. In addition, experimental lung metastasis of B16 tumor cells was significantly inhibited by rvv-mGM-CSF vaccine compared to several control vaccines when the vaccine was applied either by i.p. route (p < 0.006) or by s.c. injection (p < 0.0008). B16 cells expressing mGM-CSF after infection with rvv-mGM-CSF or transduction with a retroviral vector, were equally effective (p > 0.14) as vaccines against lung metastasis. Inhibition of metastasis was also B16 tumor cell specific. These data suggest that this approach of cancer gene therapy has a potential for use in cancer patients.
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PMID:Cancer gene therapy using tumor cells infected with recombinant vaccinia virus expressing GM-CSF. 889 77

We made several generic plasmids for construction of recombinant vaccinia virus (rvv) expressing foreign proteins in high yield. Rvvs expressing biologically active Escherichia coli beta-galactosidase (rvv-lacZ) and the cytokine murine GM-CSF (rvv-mGM-CSF) were constructed by using these plasmids. To obtain attenuated rvv, cDNA for these proteins was inserted in the thymidine kinase gene of vaccinia virus. Their expression was controlled by vaccinia early/late promoter, 7.5 K so that these proteins could be expressed in the infected cells throughout the life cycle of the virus. Female C57BL/6 mice were immunized subcutaneously with B16-F10 melanoma cells infected with rvv, and 2 weeks later challenged with viable B16 cells. Mice immunized with rvv-mGM-CSF showed delay in tumor development, smaller tumor volumes and longer survival time compared with unimmunized mice, as well as mice immunized with rvv-lacZ. Mice immunized with rvv-mGM-CSF followed by a booster injection after 1 week responded slightly better than those immunized once, but this difference was not statistically significant. These results suggested that rvv-mGM-CSF could be a promising vaccine for cancer therapy.
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PMID:Construction of recombinant vaccinia virus expressing GM-CSF and its use as tumor vaccine. 892 12

The efficacy of a recombinant vaccinia virus (rvv-GM-CSF) expressing the granulocyte macrophage colony stimulating factor (GM-CSF) as tumor vaccine was evaluated in the murine B16-F10 melanoma model. The vaccine was prepared by infection of irradiated tumor cells with rvv-GM-CSF. Control vaccine was B-16 cells infected with a recombinant vaccinia virus expressing Escherichia coli beta-galactosidase (rvv-lacZ). Pre-vaccination of naive C57BL/6 mice later inoculated with tumor cells and treatment of mice bearing tumors with GM-CSF vaccine inhibited tumor development and prolonged survival. Lung metastasis of B-16 was also inhibited by treatment with GM-CSF vaccine. The vaccine effects appeared to be tumor cell specific. The efficacy of the vaccine was comparable to a retroviral vaccine (MFG-muGM-CSF) in this system. The vaccine was also effective when rvv-GM-CSF was directly injected into the tumor. These data suggest that this vaccine approach has potential for use in cancer treatment, especially for patients with easily accessible tumors.
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PMID:Recombinant vaccinia virus expressing cytokine GM-CSF as tumor vaccine. 1065 66

Despite the overall successful application of the tet-system to regulate gene expression in vitro and in vivo, nothing is known so far about the long-term stability of this system in transgenic mice. In this study, mice of generation F2, F3, F4, or F10 of two independent tTA(CMV) transgenic lines were bred with NZL-2 mice containing a tTA-responsive bidirectional promoter that allows the simultaneous expression of two reporter genes encoding luciferase and beta-galactosidase. Analysis of the expression of transgenes in double transgenic mice revealed a dramatic reduction of tTA transactivator mRNA over time. As a consequence, the expression of both reporter genes was gradually reduced from generation to generation in tissues of embryonic and adult NZL-2/tTA(CMV) mice. Luciferase activity in NZL-2/tTA(CMV)(F10) mice was reduced 8-10-fold compared to NZL-2/ tTA(CMV)(F2) mice, and beta-galactosidase expression was no longer detectable. In summary, we describe the long-term instability of the tet-system in our NZL-2/tTA(CMV) double transgenic mice. The molecular basis of this observation and experimental tools to overcome this limitation need to be addressed in future.
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PMID:Generation dependent reduction of tTA expression in double transgenic NZL-2/tTA(CMV) mice. 1166 82