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Berlin Brandenburg

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  • 1
    In: Journal of the European Academy of Dermatology and Venereology, March 1996, Vol.6(2), pp.112-126
    Description: Since 1981, the standard therapy of herpes simplex virus infections has been based on acyclovir. Valaciclovir, the ‐valine ester of acyclovir and famciclovir, a pro‐drug of penciclovir with an improved oral bioavailability have been recently licensed. HPMPC, an acyclic nucleoside phosponate, is highly active and shows a broad range of activity against all the herpes viruses, and it is far more efficient than ganciclovir against cytomegalovirus. Ribonucleotidase inhibitors have so far been unsuccessful in the treatment of acyclovir‐resistant HSV infections. In the future, anti‐sense oligonucleotides may play a role in the therapy of herpes virus infections and many efforts continue to be made to develop vaccines which may prevent recurrences in already infected individuals. Resistance to anti‐HSV agents is almost exclusively encountered in immunocompromised patients. Failure of acyclovir therapy is mostly due to viral thymidine kinase (TK) deficiency as a result of mutation in the TK gene. Until now, the only alternatives for the treatment of acyclovir‐resistant infections have been the intravenous administration of foscarnet, frequently associated with relatively severe side effects, or the topical application of trifluridine either as single agent or in combination with interferon alpha. In vitro observations suggest that the failure of antiviral therapy is not directly due to the emergence of resistant virus isolates. Reduced uptake or activation of acyclovir may represent a selective pressure for resistant isolates in immunocompromised patients. New prodrugs with increased bioavailability, such as valaciclovir and famciclovir will perhaps prevent or delay the emergence of drug resistant isolates in immunocompromised patients since higher intracellular levels of the active compound can be achieved.
    Keywords: Acyclovir ; Famciclovir ; Valaciclovir ; Mechanism Of Action ; Antiviral Resistance
    ISSN: 0926-9959
    E-ISSN: 1468-3083
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  • 2
    Language: English
    In: FEBS Letters, 03 April 2007, Vol.581(7), pp.1317-1322
    Description: Treatment of transformed cells from leukemia or solid tumors with histone deacetylase inhibitors (HDACi) was shown to increase their sensitivity to NK cell lysis. In this study, treatment of IL-2-activated NK cells with HDACi including suberoylanilide hydroxamic acid and valproic acid was studied. Both drugs at therapeutic concentrations inhibited NK cell cytotoxicity on human leukemic cells. This inhibition was associated with decreased expression and function of NK cell activating receptors NKp46 and NKp30 as well as impaired granule exocytosis. NFκB activation in IL-2-activated NK cells was inhibited by both HDACi. Pharmacologic inhibition of NFκB activity resulted in similar effects on NK cell activity like those observed for HDACi. These results demonstrate for the first time that HDACi prevent NK cytotoxicity by downregulation of NK cell activating receptors probably through the inhibition of NFκB activation.
    Keywords: Cytotoxicity ; Nk Cells ; Histone Deacetylase Inhibitors ; Nk Cell Activating and Inhibitory Receptors ; Nuclear Factor Kappa B ; Biology ; Chemistry ; Anatomy & Physiology
    ISSN: 0014-5793
    E-ISSN: 1873-3468
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  • 3
    Language: English
    In: Cell Biology International, September 1993, Vol.17(9), pp.885-895
    Description: A protein-free chemically defined medium designated PFEK-1 was developed for culture of VERO cells on polyvinyl formal (PVF) culture surface without serum or other macromolecular supplements. VERO cells proliferated in PFEK-1 medium on PVF surface to a similar extent as cells in serum-supplemented medium without previous adaptation from serum-containing conditions. The protein-free culture infected with coxsackievirus B4, herpes simplex virus types 1 and 2, measles virus and poliovirus types 1, 2 and 3 developed viral titers comparable to those found in conventionally grown cells. The results demonstrated that VERO cells in protein-free culture provide a sensitive substrate for the production of human pathogenic viruses which are not contaminated by serum or other protein factors usually added to a culture medium.
    Keywords: Biology
    ISSN: 1065-6995
    E-ISSN: 1095-8355
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  • 4
    Language: English
    In: Cell Biology International, April 1994, Vol.18(4), pp.271-278
    Description: The effects of aphidicolin, a specific inhibitor of DNA polymerase alpha, on cell growth, DNA synthesis and myogenic differentiation in the human alveolar rhabdomyosarcoma cell line KFR were studied. The treatment with aphidicolin at 5 x 10(-6) M concentration, which completely inhibited DNA synthesis and cell growth, induced morphological differentiation of small mononuclear cells to elongated, multinucleated (myotube-like) structures. The morphological differentiation was accompanied by the expression of skeletal muscle myosin; about 30% myosin-positive cells were observed after 14 days of treatment, compared to 2.3% in untreated cultures. The results showed that aphidicolin induces differentiation of human rhabdomyosarcoma cells and that multinucleated myotube-like elements may develop simply by cell fusion without cell division and DNA synthesis.
    Keywords: Biology
    ISSN: 1065-6995
    E-ISSN: 1095-8355
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  • 5
    In: FEMS Microbiology Reviews, February 2004, Vol.28(1), pp.59-77
    Description: A high frequency of human cytomegalovirus (HCMV) genome and antigens in tumor samples of patients with different malignancies is now well documented, although the causative role for HCMV in the development of the neoplasias remains to be established. HCMV infection can modulate multiple cellular regulatory and signalling pathways in a manner similar to that of oncoproteins of small DNA tumor viruses such as human papilloma virus or adenoviruses. However, in contrast to these DNA tumor viruses, HCMV infection fails to transform susceptible normal human cells. There is now growing evidence that tumor cells with disrupted regulatory and signalling pathways enable HCMV to modulate their properties including stimulation of cell proliferation, survival, invasion, production of angiogenic factors, and immunogenic properties. In contrast to previously suggested “hit and run” transformation we suggest that persistence in tumor cells is essential for HCMV to fully express its oncomodulatory effects. These effects are observed particularly in persistent HCMV infection and are mediated mainly by activity of HCMV regulatory proteins. In persistently HCMV‐infected tumor cell lines – a selection of novel, slowly growing virus variants with changes in coding sequences for virus regulatory proteins takes place. As a result, oncomodulatory effects of HCMV infection may lead to a shift to more malignant phenotype of tumor cells contributing to tumor progression.
    Keywords: Human Cytomegalovirus ; Oncomodulation ; Tumor ; Dna‐Virus ; Apoptosis ; Angiogenesis
    ISSN: 0168-6445
    E-ISSN: 1574-6976
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