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Berlin Brandenburg

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  • MEDLINE/PubMed (NLM)  (48)
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  • 1
    Language: English
    In: BMC Research Notes, June 23, 2014, Vol.7(1)
    Description: Background Different flavonoids are known to interfere with influenza A virus replication. Recently, we showed that the structurally similar flavonoids baicalein and biochanin A inhibit highly pathogenic avian H5N1 influenza A virus replication by different mechanisms in A549 lung cells. Here, we investigated the effects of both compounds on H5N1-induced reactive oxygen species (ROS) formation and the role of ROS formation during H5N1 replication. Findings Baicalein and biochanin A enhanced H5N1-induced ROS formation in A549 cells and primary human monocyte-derived macrophages. Suppression of ROS formation induced by baicalein and biochanin A using the antioxidant N-acetyl-L-cysteine strongly increased the anti-H5N1 activity of both compounds in A549 cells but not in macrophages. Conclusions These findings emphasise that flavonoids induce complex pharmacological actions some of which may interfere with H5N1 replication while others may support H5N1 replication. A more detailed understanding of these actions and the underlying structure-activity relationships is needed to design agents with optimised anti-H5N1 activity. Keywords: H5N1, Biochanin A, Baicalein, Antiviral, Reactive oxygen species, N-acetyl-L-cysteine
    Keywords: Antiviral Agents -- Research ; Antioxidants (Nutrients) -- Research ; Avian Influenza -- Research ; Cystine ; Avian Influenza Viruses ; Macrophages
    ISSN: 1756-0500
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  • 2
    Language: English
    In: Biomaterials, 03/2010, Vol.31(8), pp.2388-2398
    Description: To link to full-text access for this article, visit this link: http://dx.doi.org/10.1016/j.biomaterials.2009.11.093 Byline: Sylvia Wagner (a), Florian Rothweiler (b), Marion G. Anhorn (c), Daniel Sauer (a), Iris Riemann (a), Eike C. Weiss (a), Alisa Katsen-Globa (a), Martin Michaelis (b), Jindrich Cinatl (b), Daniel Schwartz (d), Jorg Kreuter (c), Hagen von Briesen (a), Klaus Langer (e) Abstract: Specific transport of anti-cancer drugs into tumor cells may result in increased therapeutic efficacy and decreased adverse events. Expression of [alpha]v[beta]3 integrin is enhanced in various types of cancer and monoclonal antibodies (mAbs) directed against [alpha]v[beta]3 integrins hold promise for anti-cancer therapy. DI17E6 is a monoclonal antibody directed against [alpha]v integrins that inhibits growth of melanomas in vitro and in vivo and inhibits angiogenesis due to interference with [alpha]v[beta]3 integrins. Here, DI17E6 was covalently coupled to human serum albumin nanoparticles. Resulting nanoparticles specifically targeted [alpha]v[beta]3 integrin positive melanoma cells. Moreover, doxorubicin loaded DI17E6 nanoparticles showed increased cytotoxic activity in [alpha]v[beta]3-positive melanoma cells than the free drug. Therefore, DI17E6-coupled human serum albumin nanoparticles represent a potential delivery system for targeted drug transport into [alpha]v[beta]3-positive cells. Author Affiliation: (a) Fraunhofer Institute for Biomedical Engineering, D-66386 St.Ingbert, Germany (b) Institut fur Medizinische Virologie, Universitatsklinikum, Goethe-University, D-60590 Frankfurt, Germany (c) Institute of Pharmaceutical Technology, Biocenter of Goethe-University, D-60438 Frankfurt, Germany (d) Merck Serono, Biotech Products Development, D-64293 Darmstadt, Germany (e) Institute of Pharmaceutical Technology and Biopharmacy, Westfalische Wilhelms Universitat, Corrensstrasse 1, D-48149 Munster, Germany Article History: Received 4 November 2009; Accepted 26 November 2009
    Keywords: Drugs ; Monoclonal Antibodies ; Serum Albumin ; Anthracyclines ; Biological Products ; Integrins ; Melanoma ; Nanoparticles;
    ISSN: 01429612
    E-ISSN: 18785905
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  • 3
    In: Molecular BioSystems, 2011, Vol.7(1), pp.200-214
    Description: Chemotherapy of cancer experiences a number of shortcomings including development of drug resistance. This fact also holds true for neuroblastoma utilizing chemotherapeutics as vincristine. We performed a comparative analysis of molecular and cellular mechanisms associated with vincristine resistance utilizing cell line as well as human tissue data. Differential gene expression analysis revealed molecular features, processes and pathways afflicted with drug resistance mechanisms in general, and specifically with vincristine significantly involving actin associated features. However, specific mode of resistance as well as underlying genotype of parental, vincristine sensitive cells apparently exhibited significant heterogeneity. No consensus profile for vincristine resistance could be derived, but resistance-associated changes on the level of individual neuroblastoma cell lines as well as individual patient profiles became clearly evident. Based on these prerequisites we utilized the concept of synthetic lethality aimed at identifying hub proteins which when inhibited promise to induce cell death due to a synthetic lethal interaction with down-regulated, chemoresistance associated features. Our screening procedure identified synthetic lethal hub proteins afflicted with actin associated processes holding synthetic lethal interactions to down-regulated features individually found in all chemoresistant cell lines tested, therefore promising an improved therapeutic window. Verification of such synthetic lethal hub candidates in human neuroblastoma tissue expression profiles indicated the feasibility of this screening approach for addressing vincristine resistance in neuroblastoma.
    Keywords: Antineoplastic Agents -- Pharmacology ; Drug Resistance, Neoplasm -- Physiology ; Neoplasm Proteins -- Metabolism ; Neuroblastoma -- Metabolism ; Vincristine -- Pharmacology;
    ISSN: 1742-206X
    E-ISSN: 1742-2051
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  • 4
    Language: English
    In: Current Molecular Medicine, March 2009, Vol.9(2), pp.131-151
    Description: Highly pathogenic H5N1 avian influenza virus can infect humans and is currently the most deadly influenza virus that has crossed the species barrier. As of December 2007, the spread of H5N1 virus from human to human has been rare. Nobody can predict if H5N1 may cause a pandemic. However, the number of human cases is continuously increasing and changes in virulence and epidemiology have been detected. There are specific pathogenic features of H5N1 infection. In contrast to human-adapted influenza A strains, H5N1 preferentially infects cells of the lower respiratory tract and may spread to tissues outside the respiratory tract in humans. Moreover, H5N1 replication is prolonged in target organs and results in higher viral loads and increased tissue damage. These features will have to be considered for therapeutic protocols for H5N1 infection in humans. Rapid genetic and antigenic changes observed in H5N1 virus isolates represent a challenge for the development of vaccines. In the present review, current knowledge about epidemiology, virulence factors and pathology of H5N1 infections in humans are summarised and discussed. Moreover, the possible roles of antiinfluenza drugs in the pandemic situation as well as the development of effective vaccines are subject of this overview.
    Keywords: Pathogenic H5n1 ; Avian Influenza ; Humans ; Of Chickens ; Epidemiology ; Epidemiology
    ISSN: 1566-5240
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  • 5
    Language: English
    In: Int. Journal of Clinical Pharmacology and Therapeutics, 2017, Vol.55(08), pp.686-689
    Keywords: A549 Cells–Therapeutic Use ; Antineoplastic Agents–Drug Therapy ; Carcinoma, Non-Small-Cell Lung–Therapeutic Use ; Cell Line, Tumor–Drug Effects ; Cisplatin–Genetics ; Humans–Drug Effects ; Signal Transduction–Genetics ; Transcriptome–Genetics ; Antineoplastic Agents ; Cisplatin;
    ISSN: 0946-1965
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  • 6
    Language: English
    In: Oncology Letters, 11/2017, Vol.14(5), pp.5513-5518
    Description: Treatment failure in metastatic bladder cancer is commonly caused by acquisition of resistance to chemotherapy in association with tumor progression. Since alterations of integrins can influence the adhesive and invasive behaviors of urothelial bladder cancer cell lines, the present study aimed to evaluate the role of integrins in bladder cancer cells with acquired resistance to standard first-line chemotherapy with gemcitabine, and cisplatin. Therefore, four gemcitabine- and four cisplatin-resistant sublines out of a panel of four parental urothelial bladder cancer cell lines (TCC-SUP, HT1376, T24, and 5637) were used. Expression of integrin subunits α3, α5, α6, β1, β3, and β4 was detected using flow cytometry. Adhesion and chemotaxis were analyzed. For functional assays, integrin β1 was attenuated with a blocking antibody. In untreated cells, chemotaxis was upregulated in 3/4 gemcitabine-resistant sublines. In cisplatin-resistant cells, chemotaxis was enhanced in 2/4 cell lines. Acquired chemoresistance induced the upregulation of integrin β1 in all four tested gemcitabine-resistant sublines, as well as an upregulation in 3/4 cisplatin-resistant sublines compared with parental cell lines. Following the inhibition of integrin β1, adhesion to extracellular matrix components was downregulated in 3/4 gemcitabine-resistant sublines and in all four tested cisplatin-resistant sublines. Since integrin β1 is frequently upregulated in chemoresistant urothelial cancer cell lines and inhibition of integrin β1 may influence adhesion, further studies are warranted to evaluate integrin β1 as a potential therapeutic target for bladder cancer in vivo .
    Keywords: Adhesion ; Acquired Resistance ; Cancer Cell Line Collection ; Chemotaxis ; Cisplatin ; Gemcitabine ; Integrin Β1 ; Urothelial Cancer
    ISSN: 1792-1074
    E-ISSN: 1792-1082
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  • 7
    Language: English
    In: Medical Microbiology and Immunology, 2007, Vol.196(4), pp.213-225
    Description: Among emerging and re-emerging infectious diseases, influenza constitutes one of the major threats to mankind. In this review series epidemiologic, virologic and pathologic concerns raised by infections of humans with avian influenza virus A/H5N1 are discussed. This fourth part focuses on vaccine development. Several phase I clinical studies with vaccines against H5 viruses have demonstrated limited efficacy compared to seasonal influenza vaccines. To induce protective immunity two immunisations with increased amounts of H5N1 vaccine were required. Novel vaccination strategies that are egg- and adjuvant-independent, broadly cross-reactive and long-lasting are highly desirable.
    Keywords: Vaccines ; Avian Influenza;
    ISSN: 0300-8584
    E-ISSN: 1432-1831
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  • 8
    Language: English
    In: The Journal of Infectious Diseases, 09/2000, Vol.182(3), pp.643-651
    Description: In fibroblasts, infection with human cytomegalovirus (HCMV) inhibits expression of the extracellular matrix proteins thrombospondin-1 and -2 (TSP-1 and TSP-2). These effects may depend on expression of HCMV immediate-early (IE) genes, which are activated by cellular transcription factor NF-kappaB. The influence of HCMV infection on TSP-1 and TSP-2 expression and the ability of different antiviral drugs to prevent these cellular changes in permissive cultures of human retinal glial cells were observed. Ganciclovir inhibited only HCMV late antigen (LA) expression, whereas antisense oligonucleotide ISIS 2922 and peptide SN50, inhibitors of HCMV IE expression and NF-kappaB activity, respectively, inhibited both IE and LA expression. ISIS 2922 and SN50, but not ganciclovir, prevented down-modulation of TSP-1 and TSP-2. The results showed that HCMV-induced down-modulation of TSP-1 and TSP-2 in retinal glial cells is prevented by inhibition of HCMV IE expression. These findings may be relevant to pathogenesis and treatment of HCMV retinitis.
    Keywords: Antiviral Agents -- Pharmacology ; Cytomegalovirus Retinitis -- Metabolism ; Neuroglia -- Metabolism ; Retina -- Metabolism ; Thrombospondin 1 -- Biosynthesis ; Thrombospondins -- Biosynthesis;
    ISSN: 0022-1899
    E-ISSN: 1537-6613
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  • 9
    Article
    Article
    In: Current Pharmaceutical Design, November 2007, Vol.13(33), pp.3378-3393
    Description: The short chain fatty acid valproic acid (VPA, 2-propylpetanoic acid) is approved for the treatment of epilepsia, bipolar disorders and migraine and clinically used for schizophrenia. In 1999, the first clinical anti-cancer trial using VPA was initiated. Currently, VPA is examined in numerous clinical trials for different leukaemias and solid tumour entities. In addition to clinical assessment, the experimental examination of VPA as anti-cancer drug is ongoing and many questions remain unanswered. Although other mechanisms may also contribute to VPA-induced anti-cancer effects, inhibition of histone deacetylases appears to play a central role. This review focuses on recent developments regarding the anti-cancer activity of VPA.
    Keywords: Hdac ; Differentiation ; Combination Therapy ; Clinical Studies ; Valproic Acid ; Angiogenesis
    ISSN: 1381-6128
    E-ISSN: 18734286
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  • 10
    Language: English
    In: International journal of pharmaceutics, 2011, Vol.415(1), pp.244-251
    Description: Glioblastomas belong to the most devastating cancer diseases. For this reason, polysorbate 80 (Tween 80®)-coated poly(isohexyl cyanoacrylate) (PIHCA) (Monorex®) nanoparticles loaded with doxorubicin were developed and tested for their use for the treatment of glioblastomas. The preparation of the nanoparticles resulted in spherical particles with high doxorubicin loading. The physico-chemical properties and the release of doxorubicin from the PIHCA-nanoparticles were analysed, and the influence on cell viability of the rat glioblastoma 101/8-cell line was investigated. In vitro, the empty nanoparticles did not show any toxicity, and the anti-cancer effects of the drug-loaded nanoparticles were increased in comparison to doxorubicin solution, represented by IC₅₀ values. The in vivo efficacy was then tested in intracranially glioblastoma 101/8-bearing rats. Rats were treated with 3×1.5mg/kg doxorubicin and were sacrificed 18 days after tumour transplantation. Histological and immunohistochemical analyses were carried out to assess the efficacy of the nanoparticles. Tumour size, proliferation activity, vessel density, necrotic areas, and expression of glial fibrillary acidic protein demonstrated that doxorubicin-loaded PIHCA-nanoparticles were much more efficient than the free drug. The results suggest that poly(isohexyl cyanoacrylate) nanoparticles hold great promise for the non-invasive therapy of human glioblastomas. ; p. 244-251.
    Keywords: Therapeutics ; Doxorubicin ; Toxicity ; Cell Viability ; Immunohistochemistry ; Polysorbates ; Physicochemical Properties ; Neoplasms ; Inhibitory Concentration 50 ; Humans ; Rats ; Nanoparticles
    ISSN: 0378-5173
    E-ISSN: 18733476
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