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  • 1
    Language: English
    In: Antiviral Research, 2001, Vol.49(3), pp.129-145
    Description: The replication cycle of the human cytomegalovirus (HCMV) is characterized by the expression of immediate early (IE), early (E), and late (L) gene regions. Current antiviral strategies are directed against the viral DNA polymerase expressed during the early phase of infection. The regulation of the IE-1 and IE-2 gene expression is the key to latency and active replication due to their transactivating and repressing functions. There is growing evidence that the pathogenic features of HCMV are largely due to the abilities of IE-1 and IE-2 to transactivate cellular genes. Consequently, current drugs used to inhibit HCMV infection would have no impact on IE-1 and IE-2-induced effects that are produced before the early phase. Moreover, when HCMV DNA replication is inhibited, IE gene products accumulate in infected cells causing disturbances of host cell functions. This review summarizes the biological functions of HCMV-IE gene expression, their relevance in pathogenesis, as well as efforts to develop novel treatment strategies directed against HCMV-IE expression.
    Keywords: Cytomegalovirus ; Immediate Early Gene Expression ; Immunopathomechanisms ; Antiviral Therapy ; Medicine ; Biology
    ISSN: 0166-3542
    E-ISSN: 1872-9096
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  • 2
    In: Anti-Cancer Drugs, 2001, Vol.12(5), pp.467-473
    Description: Treatment failure in most neuroblastoma (NB) patients is related to primary and/or acquired resistance to conventional chemotherapeutic agents. Aphidicolin (APH), a tetracyclic diterpene, exhibits specific cytotoxic action against NB cells. The purpose of this study was to compare antitumoral efficacy of APH in parental NB cell lines and cell subclones that exhibit drug resistance to vincristine (VCR), doxorubicin (DOX) and cisplatin. Due to poor solubility of APH in water, γ-cyclodextrin (γ-CD) inclusion complexes of APH were used for systemic treatment of xenotransplanted parental and VCR-resistant UKF-NB-3 tumours. APH and its γ-CD inclusion complexes inhibited growth of parental and drug-resistant NB cells at equimolar doses in vitro. Growth of VCR-sensitive and -resistant NB tumors was inhibited at equal doses in a dose-dependent fashion in vivo. These results indicate that the specific cytotoxic activity of APH against NB cells in vitro and in vivo is independent of cellular mechanisms facilitating drug resistance to conventional chemotherapeutic drugs. Hence, taking into account our previous findings that APH acts synergistically with VCR and DOX, APH might be an additive tool for the therapy of NB and is suitable for evaluation in clinical studies of NB treatment protocols.
    Keywords: Aphidicolin -- Therapeutic Use ; Cell Survival -- Drug Effects ; Cyclodextrins -- Pharmacology ; Enzyme Inhibitors -- Therapeutic Use ; Neuroblastoma -- Drug Therapy ; Tumor Cells, Cultured -- Drug Effects;
    ISSN: 0959-4973
    E-ISSN: 14735741
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