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Berlin Brandenburg


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  • Klassert, D  (6)
Type of Medium
  • 1
    Language: English
    In: Science, 2012, Vol.336(6079), pp.344-347
    Description: Recent studies have shown that the polar bear matriline (mitochondrial DNA) evolved from a brown bear lineage since the late Pleistocene, potentially indicating rapid speciation and adaption to arctic conditions. Here, we present a high-resolution data set from multiple independent loci across the nuclear...
    Keywords: Medicin Och Hälsovetenskap ; Klinisk Medicin ; Neurologi ; Medical And Health Sciences ; Clinical Medicine ; Neurology ; Medicin Och Hälsovetenskap ; Klinisk Medicin ; Kirurgi ; Medical And Health Sciences ; Clinical Medicine ; Surgery
    ISSN: 1095-9203
    ISSN: 00368075
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  • 2
    In: Wound Repair and Regeneration, September 2011, Vol.19(5), pp.597-607
    Description: The pathophysiology leading to delayed wound healing is complex and efficient therapeutic approaches for accelerated wound healing currently do not exist. We developed a novel drug‐eluting platform for the potential use in wound dressings. Here, we report on the potential of eluting ascorbic acid‐2‐phosphate (‐2), a highly stable variant of ascorbic acid, to induce angiogenesis and to promote collagen synthesis by fibroblasts. The drug‐eluting platform device () consists of biocompatible polymeric layers comprising polyethylene terephtalate, polyvinyl alcohol (), and polyurethane with as the solvent for ‐2. The angiogenic potential of ‐2 was evaluated in the endothelial cell tube formation assay () and in the chorion allantoic membrane () model. Collagen synthesis by ‐2‐stimulated fibroblasts was determined by irius ed staining. ‐2 significantly induced angiogenesis in five independent and assays and induced collagen synthesis in two different fibroblast cell lines. The eluting kinetics of ‐2 was determined by the ultraviolet anorop method and the functional 2,2′‐Azinobis‐(3‐ethylbenzthiazolin‐6‐sulfonic acid) method. Eluting profiles showed a continuous release in the range of biologically effective concentrations 〉10 days. This is the first report showing the proangiogenic‐ and collagen‐promoting features of ‐2. loaded with ‐2 ought to be further evaluated as wound dressings or as supplementary pads for topical treatment of delayed wound healing in preclinical studies.
    Keywords: Drug Delivery Systems ; Angiogenesis Inducing Agents -- Pharmacology ; Ascorbic Acid -- Analogs & Derivatives ; Neovascularization, Physiologic -- Drug Effects ; Wound Healing -- Drug Effects;
    ISSN: 1067-1927
    E-ISSN: 1524-475X
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  • 3
    Language: English
    In: Molecular Cancer, 2009, Vol.8(1), pp.urn:issn:1476-4598
    Description: Background: Chemoresistance acquisition may influence cancer cell biology. Here, bioinformatics analysis of gene expression data was used to identify chemoresistance-associated changes in neuroblastoma biology. Results: Bioinformatics analysis of gene expression data revealed that expression of angiogenesis-associated...
    Keywords: Endothelial Growth-Factor ; In-Vivo ; Melanoma-Cells ; Tumor-Growth ; N-Myc ; Extracellular-Matrix ; Angiogenic Factors ; Cytokine Network ; Vegf Expression ; Blood-Vessels
    ISSN: 1476-4598
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  • 4
    Language: English
    In: Investigative ophthalmology & visual science, November 2009, Vol.50(11), pp.5419-25
    Description: Ocular involvement in influenza A virus diseases is common but usually limited to mild conjunctivitis. Rarely, inflammation of the choriocapillaris may result in atrophia of the retinal pigment epithelium (RPE). Primary human retinal pigment epithelial (RPE) cells were infected with seasonal (H1N1 A/New Caledonia/20/99, H3N2 A/California/7/2004) or highly pathogenic avian H5N1 (A/Thailand/1(Kan-1)/04, A/Vietnam/1203/04, A/Vietnam/1194/04) influenza strains. Influenza A virus replication was studied by investigation of cytopathogenic effects, immune staining for influenza A virus nucleoprotein, determination of virus titers, and electron microscopy. Apoptosis induction was examined by immune staining for activated caspase 3 and cleaved PARP. Proinflammatory gene expression was investigated by quantitative PCR. H5N1 but not seasonal influenza strains replicated to high titers (〉10(8) TCID(50)/mL; 50% tissue culture infectious dose/milliliter) in RPE cells. H5N1 infection resulted in RPE cell apoptosis that was abolished by the antiviral drug ribavirin. Pretreatment with type I interferons (interferon-alpha and -beta) or the type II interferon, (interferon-gamma), inhibited H5N1 replication. Moreover, H5N1 infection induced expression of proinflammatory genes (tumor necrosis factor-alpha, CXCL8, CXCL10, CXCL11, and interleukin-6), which was inhibited by ribavirin in a concentration-dependent manner. A novel cell type derived from the central nervous system was permissive to H5N1 influenza virus replication. This findings supports those suggesting H5N1 influenza strains to own a greater potential to spread to nonrespiratory tissues than seasonal human influenza viruses. Moreover, the data warrant the further study of the role of influenza A virus replication in retinal diseases associated with influenza A virus infections.
    Keywords: Influenza A Virus, H1n1 Subtype -- Physiology ; Influenza A Virus, H2n2 Subtype -- Physiology ; Influenza A Virus, H5n1 Subtype -- Physiology ; Retinal Pigment Epithelium -- Virology ; Virus Replication -- Physiology
    E-ISSN: 1552-5783
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  • 5
    Language: English
    In: Neoplasia, December 2008, Vol.10(12), pp.1402-1410
    Description: Prolonged treatment of leukemic cells with chemotherapeutic agents frequently results in development of drug resistance. Moreover, selection of drug-resistant cell populations may be associated with changes in malignant properties such as proliferation rate, invasiveness, and immunogenicity. In the present study, the sensitivity of cytarabine (1-β- -arabinofuranosylcytosine, araC)-resistant and parental human leukemic cell lines (T-lymphoid H9 and acute T-lymphoblastic leukemia Molt-4) to natural killer (NK) cell-mediated killing was investigated. The results obtained demonstrate that araC-resistant H9 and Molt-4 (H9 ARAC and Molt-4 ARAC ) cell lines are more sensitive to NK cell-mediated lysis than their respective parental cell lines. This increased sensitivity was associated with a higher surface expression of ligands for the NK cell-activating receptor NKG2D, notably UL16 binding protein-2 (ULBP-2) and ULBP-3 in H9 ARAC and Molt-4 ARAC cell lines. Blocking ULBP-2 and ULBP-3 or NKG2D with monoclonal antibody completely abrogated NK cell lysis. Constitutive phosphorylated extracellular signal-regulated kinase (ERK) but not pAKT was higher in araC-resistant cells than in parental cell lines. Inhibition of ERK using ERK inhibitor PD98059 decreased both ULBP-2/ULBP-3 expression and NK cell cytotoxicity. Furthermore, overexpression of constitutively active ERK in H9 parental cells resulted in increased ULBP-2/ULBP-3 expression and enhanced NK cell lysis. These results demonstrate that increased sensitivity of araC-resistant leukemic cells to NK cell lysis is caused by higher NKG2D ligand expression, resulting from more active ERK signaling pathway.
    Keywords: Medicine
    ISSN: 1476-5586
    E-ISSN: 1476-5586
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  • 6
    Language: English
    In: Cancer research, 15 January 2009, Vol.69(2), pp.416-21
    Description: Murine double minute 2 (MDM2) negatively regulates the activity of the tumor suppressor protein p53. Nutlin-3 is a MDM2 inhibitor under preclinical investigation as nongenotoxic activator of the p53 pathway for cancer therapy. Here, nutlin-3 was evaluated for its activity alone or in combination with established chemotherapeutic drugs for antitumor action in chemosensitive and chemoresistant neuroblastoma and rhabdomyosarcoma cell lines. Effects of nutlin-3 single treatment were much more pronounced in p53 wild-type cell lines (IC(50)s 17 micromol/L). In sharp contrast to the expectations, nutlin-3 concentrations that did not affect viability of p53-mutated cell lines strongly increased the efficacy of vincristine in p53-mutated, P-glycoprotein (P-gp)-overexpressing cell lines (decrease in IC(50)s 92- to 3,434-fold). Similar results were obtained for other P-gp substrates. Moreover, nutlin-3 reduced efflux of rhodamine 123 and other fluorescence dyes that are effluxed by P-gp. Investigation of Madin-Darby canine kidney (MDCK) II cells stably transfected with plasmids encoding for P-gp (MDCKII MDR1) or multidrug resistance protein 1 (MRP-1, MDCKII MRP1) revealed that nutlin-3 not only interferes with P-gp but also affects MRP-1-mediated efflux. Kinetic studies and investigation of P-gp-ATPase activity showed that nutlin-3 is likely to act as a P-gp transport substrate. Examination of the nutlin-3 enantiomers nutlin-3a and nutlin-3b revealed that, in contrast to MDM2-inhibitory activity that is limited to nutlin-3a, both enantiomers similarly interfere with P-gp-mediated drug efflux. In conclusion, nutlin-3-induced inhibition of P-gp and MRP-1 was discovered as a novel anticancer mechanism of the substance in this report.
    Keywords: ATP Binding Cassette Transporter, Subfamily B, Member 1 -- Antagonists & Inhibitors ; Antineoplastic Combined Chemotherapy Protocols -- Pharmacology ; Imidazoles -- Pharmacology ; Neuroblastoma -- Drug Therapy ; Piperazines -- Pharmacology ; Rhabdomyosarcoma, Alveolar -- Drug Therapy
    ISSN: 00085472
    E-ISSN: 1538-7445
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