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

The efficacy of adenovirus-mediated gene therapy for treatment of metastatic B16 melanomas, established in syngeneic C57BL/6 mice, was assessed via an ex vivo cytokine vaccine approach or via an in vivo strategy utilizing combination cytokine/herpes simplex virus-thymidine kinase (HSV-tk) suicide gene delivery and treatment with ganciclovir (GCV). In the ex vivo tumor vaccine approach, B16 melanoma cells, transduced in vitro by adenovirus containing either interleukin (IL)-2, granulocyte-macrophage colony stimulating factor (GM-CSF), or tumor necrosis factor-alpha cytokine genes and gamma irradiated, were subcutaneously injected into the flank and a distant subcutaneous challenge injection of unmodified B16 melanoma cells was performed 15 d later. Significant reductions in challenge tumor volume were observed in the IL-2 group (75% reduction; p = 0.02) and in the GM-CSF group (88% reduction; p = 0.0006), whereas the effect for tumor necrosis factor-alpha was not statistically significant. In the in vivo treatment of established melanomas, this cytokine approach was combined with a suicide gene therapy and subcutaneous B16 melanomas were directly injected with (i) IL-2/recombinant, replication-deficient adenovirus (adv) and thymidine kinase (tk)/adv, (ii) GM-CSF/adv, IL-2/adv, and tk/adv, or (iii) control beta-galactosidase (beta-gal)/adv and tk/adv. After intraperitoneal application of GCV (10 mg per kg) for 6 d, the residual tumor masses were excised and the animals challenged with unmodified B16 cells. Challenge tumor growth was reduced by 56% for the IL-2/tk/adv/GCV treatment (p = 0.041) and by 77% for the GM-CSF/IL-2/tk/adv/GCV treatment p (p = 0.037), in comparison with the beta-gal/tk/GCV control group. These data may hold significant promise for the development of effective ex vivo and in vivo gene therapy modalities to counter the highly metastatic nature of human melanoma.
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PMID:Ex vivo and in vivo adenovirus-mediated gene therapy strategies induce a systemic anti-tumor immune defence in the B16 melanoma model. 962 Feb 91

Cationic liposomes containing the human interferon-beta (IFN-beta) gene induce marked growth inhibition in human glioma cells. In vivo experiments using an human glioma implanted into the brains of nude mice have demonstrated a definite growth-inhibitory effect, achieving complete tumor regression with multiple intratumoral injections of the gene. However, nude mouse studies are inadequate to evaluate antitumor effects fully, especially those related to activation of the host immune response. This article aimed to investigate antitumor effects and immune response activation by murine IFN-beta gene transfer in syngeneic mice. In vitro experiments demonstrated a stronger growth-inhibitory effect of liposomes containing the murine IFN-beta gene on a GL261 mouse glioma cell line than exogenously added murine IFN-beta. In in vivo experiments, intratumoral administration of liposomes containing the murine IFN-beta gene resulted in a 16-fold reduction in the mean volume of residual gliomas in the brains of C57BL/6 mice and massive infiltration of cytotoxic T lymphocytes (CTL) within the residual tumor, while few CTL were infiltrated in controls including murine IFN-beta, empty liposomes, naked plasmid expressing murine IFN-beta, and liposomes containing beta-galactosidase gene. In addition, 40% of mice treated with liposomes containing the murine IFN-beta gene were completely cured. These findings indicated that activation of cellular immunity participates in antitumor effects in vivo together with direct effects of the IFN-beta gene.
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PMID:Antitumor effect and cellular immunity activation by murine interferon-beta gene transfer against intracerebral glioma in mouse. 1049 Jul 73

Derivatives of the Edmonston-B strain of measles virus (MV-Ed) are safe, live attenuated measles virus (MV) vaccines that have been used worldwide for more than 30 years. The cytoreductive potential of MV-Ed has been investigated in murine models of both aggressive and indolent B-cell lymphoma in severe combined immunodeficient (SCID) mice. The rationale for these studies was generated by experience with viral fusogenic membrane glycoproteins as cytotoxic genes and the recognition of the potential of replicating viruses in the treatment of human malignancy. Intratumoral injection of both unmodified MV-Ed and a strain of MV-Ed genetically modified by the addition of a beta-galactosidase reporter gene (MVlacZ) induced regression of large established human lymphoma xenografts, in contrast to control therapy with UV-inactivated virus, in which all tumors progressed. The antitumor effect still occurred in the presence of passively transferred anti-MV antibody. Intravenous administration of MV also resulted in considerable slowing of tumor progression. Analysis of sections of residual tumor confirmed replication of MV within the tumors. Thus, the vaccine strain of MV mediates regression of large, established human B-cell lymphoma xenografts in SCID mice, and proof of principle is established that MV is oncolytic for lymphomas in vivo. Attenuated MVs may have value as a novel replicating-virus therapy for this group of disorders. (Blood. 2001;97:3746-3754)
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PMID:Live attenuated measles virus induces regression of human lymphoma xenografts in immunodeficient mice. 1138 12