Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: RECEPTOR ; CELLS ; ENDOTHELIAL-CELLS ; CELL ; Germany ; human ; PROTEIN ; PROTEINS ; DRUG ; cell line ; LINES ; FAMILY ; tumour ; BINDING ; CELL-LINES ; MEMBER ; MEMBERS ; antibodies ; antibody ; TARGET ; IDENTIFICATION ; PLASMA ; Western-blot ; MEMBRANE ; SPECTROMETRY ; CELL-LINE ; LINE ; PURIFICATION ; SURFACE ; isolation ; AFFINITY ; ARGININE METHYLATION ; BRUSH-BORDER ; CONFORMATIONALLY MODIFIED ALBUMINS ; LUNG-CANCER DETECTION ; METHOTREXATE-ALBUMIN ; TREATED SERUM-ALBUMIN ; CALRETICULIN ; albumin-binding proteins (ABPs) ; heterogeneous nuclear ribonucleoproteins (hnRNP) ; crossl
    Abstract: Since albumin is being developed as a drug carrier to target tumours the search for albumin-binding proteins (ABPs), which play a role in cell surface binding and endocytosis of native and conjugated albumins becomes more and more interesting. We isolated five different proteins from purified plasma membranes from three different human tumour cell lines (CCRF-CEM, MV3 and MCF7) by albumin affinity chromatography and identified them as four members of the heterogeneous nuclear ribonucleoproteins (hnRNP) family and calreticulin by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry. Contamination of the plasma membrane preparation by nuclear membranes was excluded with anti-nucleopore antibodies. Western blot analyses of plasma membranes showed ABPs with the same molecular weights as the albumin-affinity isolates. Tryptic digestion of intact cells was used to determine the sidedness of the albumin-binding property, which is oriented to the exterior of the cell. Localisation to the plasma membrane and albumin binding is a novel property of hnRNP. (C) 2003 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 14757165
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: APOPTOSIS ; CANCER ; CELLS ; GROWTH ; CELL ; human ; INHIBITION ; DNA adducts ; DRUG ; METABOLISM ; LINES ; NEUROBLASTOMA-CELLS ; DNA ; MECHANISM ; DNA ADDUCT FORMATION ; INDUCTION ; cell cycle ; CELL-LINES ; treatment ; HUMANS ; BIOSYNTHESIS ; CELL-LINE ; fragmentation ; ADDUCTS ; cell lines ; CYTOTOXICITY ; neuroblastoma ; AGENT ; DNA-ADDUCTS ; cell survival ; DNA ADDUCT ; pharmacology ; cyclooxygenase 2 ; Cell Line,Tumor ; anticancer drug ; ANTICANCER DRUG ELLIPTICINE ; ellipticine ; drug effects ; peroxidases ; Antineoplastic Agents ; Cytochrome P-450 Enzyme System ; Ellipticines ; peroxidase ; ANTICANCER ; CANCER-CELL-LINES ; Topoisomerase ; Chromatography,High Pressure Liquid ; Cyclooxygenase 1 ; Dose-Response Relationship,Drug
    Abstract: Ellipticine is an antineoplastic agent, whose mode of action is based mainly on DNA intercalation, inhibition of topoisomerase II and formation of covalent DNA adducts mediated by cytochromes P450 and peroxidases. Here, the molecular mechanism of DNA-mediated ellipticine action in human neuroblastoma IMR-32, UKF-NB-3 and UKF-NB-4 cancer cell lines was investigated. Treatment of neuroblastoma cells with ellipticine resulted in apoptosis induction, which was verified by the appearance of DNA fragmentation, and in inhibition of cell growth. These effects were associated with formation of two covalent ellipticine-derived DNA adducts, identical to those formed by the cytochrome
    Type of Publication: Journal article published
    PubMed ID: 19426684
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: RECEPTOR ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; GROWTH-FACTOR ; CELL ; FACTOR RECEPTOR ; Germany ; INHIBITION ; KINASE ; PATHWAY ; PATHWAYS ; THERAPY ; TYROSINE KINASE ; GENE-EXPRESSION ; ACTIVATION ; DNA ; BIOLOGY ; cell cycle ; CELL-CYCLE ; CYCLE ; signal transduction ; TYROSINE KINASE INHIBITOR ; VARIANTS ; TARGET ; IDENTIFICATION ; LESIONS ; microarrays ; VECTOR ; DAMAGE ; CANCER-CELLS ; DNA-DAMAGE ; systems biology ; CANCER-THERAPY ; EPIDERMAL-GROWTH-FACTOR ; HUMAN GLIOBLASTOMA CELLS ; INHIBITORS ; VARIANT ; SCIENCE ; EGFR ; DNA damage ; pharmacogenomics ; pharmacology ; oncogenes ; HYDROCARBON RECEPTOR ; pharmacognosy ; LINDERA-MEGAPHYLLA ; tumours ; FACTOR-RECEPTOR ; natural product ; ALPHA-1-ADRENOCEPTOR ANTAGONIST ; APORPHINE ALKALOIDS ; CASSYTHA-FILIFORMIS ; DRUG-SENSITIVITY ; GLAUCIUM-FLAVUM-GRANTZ ; HUMAN LEUKEMIC-CELLS ; TOPOISOMERASE-I INHIBITOR
    Abstract: The extraordinary relevance of EGFR in turnout biology makes it an exquisite molecular target for tumour therapy. Despite considerable success with these EGFR tyrosine kinase inhibitors in cancer therapy, resistance against these chemical compounds develops owing to the selection of point-mutated variants of EGFR. Therefore, there is an urgent need for the identification of novel EGFR tyrosine kinase inhibitors for treating tumours with such EGFR mutants. We found a preferential cytotoxicity of dicentrine towards U87MG.Delta EGFR-transduced with a constitutively deletion-activated EGFR expression vector as compared to non-transduced wild-type U87MG cells. As determined by microarray-based mRNA expression profiling, this preferential cytotoxicity was accompanied with an activation of BRCA1-mediated DNA damage response, p53 signalling, G1/S and G2/M cell cycle regulation, and aryl hydrocarbon receptor pathways. The activation of these signalling routes might be explained by the fact that dicentrine intercalates DNA and induces DNA strand break by inhibition of DNA topoisomerases. The cell cycle might be arrested by dicentrine-induced DNA lesions. (C) 2009 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 20005213
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: RECEPTOR ; EXPRESSION ; GROWTH ; IN-VITRO ; INHIBITOR ; CELL ; Germany ; INHIBITION ; PATHWAY ; PATHWAYS ; DISEASE ; GENE ; GENE-EXPRESSION ; GENES ; microarray ; PROTEIN ; METABOLISM ; LINES ; NF-KAPPA-B ; NITRIC-OXIDE ; MACROPHAGES ; TARGET ; MOUSE ; ASSAY ; microarrays ; NECROSIS-FACTOR-ALPHA ; CELL-LINE ; LINE ; PROGNOSTIC VALUE ; TARGETS ; inflammation ; CYTOTOXICITY ; INCREASED EXPRESSION ; INHIBITORS ; CELL-GROWTH ; signaling ; INTERFERENCE ; SCIENCE ; pharmacology ; nitric oxide ; NITROSATIVE STRESS ; INTERLEUKIN-10 ; TUMOR BIOLOGY ; NATURAL-PRODUCTS ; POOR SURVIVAL ; natural product ; Glucocorticoid receptor signaling pathway ; Griess assay ; Interleukin-10 signaling pathway ; RAW-264.7 CELLS ; THIOREDOXIN SYSTEM
    Abstract: Nitric oxide (NO) plays a role in various physiological and pathophysiological conditions such as immunoregulatory and inflammatory processes. Hence, NO and its generating enzyme, inducible nitric oxide synthase (iNOS) may not only be of diagnostic and prognostic value, but may also serve as targets for novel therapeutic options. In the present investigation, we have screened a phytochemical library by correlating the IC50 values for 531 natural products of 60 cell lines with the microarray-based mRNA expression of 95 genes known to be involved in NO metabolism and signaling with the aim to identify candidate compounds as inhibitors for NO metabolism and signaling. We identified bis(helenalinyl)glutarate (BHG) as putative candidate compound. Indeed. BHG inhibited NO production (IC50 value: 0.90 +/- 0.04 mu M) and down-regulated iNOS protein expression (IC50 value: 1.12 +/- 0.16 mu M) of RAW264.7 mouse macrophages in the presence of lipopolysaccharide. Performing XTT cytotoxicity assays, we found that BHG inhibited cell growth in a dose-dependent manner with an IC50 value of 5.6 mu M. To gain insight into molecular pathways involved in NO inhibition and cytotoxicity, we performed microarray experiments which were exemplarily validated by real-time RT-PCR. A total of 227 genes (67 up- and 160 down-regulated) were obtained, which exhibited significant differences in mRNA regulation between BHG-treated and untreated RAW264.7 macrophages. Sixteen of 227 genes are known to be involved in NO-signaling. Pathway analyses revealed that further five and four down-regulated genes belong to the glucocorticoid receptor and interleukin-1 and interleukin-10 pathways, respectively. An interference of these two pathways and NO is known for inflammation and auto-immune diseases. The therapeutic potential of this compound has to be explored in the future. (C) 2010 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 20105431
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; PATHWAY ; GENE ; GENE-EXPRESSION ; GENES ; chemotherapy ; OXIDATIVE STRESS ; MULTIDRUG-RESISTANCE ; AMINO-ACID-SEQUENCE ; neuroblastoma ; chemoresistance ; traditional Chinese medicine ; LEUKEMIA-CELLS ; artemisinin ; artesunate ; EXPRESSION PROFILES ; pharmacology ; FALCIPARUM-MALARIA ; GAMMA-GLUTAMYLCYSTEINE SYNTHETASE ; ASCITES TUMOR-CELLS ; CYTOTOXIC ACTION
    Abstract: Artemisinin derivatives are well-tolerated anti-malaria drugs that also exert anti-cancer activity. Here, we investigated artemisinin and its derivatives dihydroartemisinin and artesunate in a panel of chemosensitive and chemoresistant human neuroblastoma cells as well as in primary neuroblastoma cultures. Only dihydroartemisinin and artesunate affected neuroblastoma cell viability with artesunate being more active. Artesunate-induced apoptosis and reactive oxygen species in neuroblastoma cells. Of 16 cell lines and two primary cultures, only UKF-NB-3(r)CDDP(1000) showed low sensitivity to artesunate. Characteristic gene expression signatures based on a previous analysis of artesunate resistance in the NC160 cell line panel clearly separated UKF-NB-3(r)CDDP(1000) from the other cell lines. L-Buthionine-S,R-sulfoximine, an inhibitor of GCL (glutamate-cysteine ligase), resensitised in part UKF-NB-3(r)CDDP(1000) cells to artesunate. This finding together with bioinformatic analysis of expression of genes involved in glutathione metabolism showed that this pathway is involved in artesunate resistance. These data indicate that neuroblastoma represents an artesunate-sensitive cancer entity and that artesunate is also effective in chemoresistant neuroblastoma cells. (C) 2009 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 19698702
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    Keywords: PATHWAY ; GENE ; transcription ; T-CELLS ; ANTIGEN-PRESENTING CELLS ; KAPPA-B ; CD40 ; IMMUNE-SYSTEM ; MYELOFIBROSIS ; JAK2 INHIBITOR
    Abstract: Inhibition of Janus-activated kinase-1 (JAK1) is a promising clinical concept for post-transplant immunosuppression and autoimmunity. However, it also raises concerns regarding possible immunosuppressive side effects. Our study investigates JAK1 signalling in the context of CD40L and bacterially activated human MoDC using siRNA and biological inhibitors. We demonstrate that strong stimuli (e.g. intact Escherichia coli or LPS in addition to IL-1beta) induce IL-12p70 via a ROS/RELA/CDK9 pathway that is inhibited by simultaneous JAK1/STAT3 signalling. Transcription is effective if RELA recruits the positive transcription elongation factor b (P-TEFb) component CDK9 to a combined RELA/STAT3 binding site -50 to -20bp upstream of the start site of the IL-12p35 promoter. STAT3 simultaneously attaches to this site and inhibits CDK9 binding. In the presence of IFNgamma, JAK1/2 inhibitors block STAT1/IRF1/IRF8-dependent activation and simultaneously enhance CDK9-dependent activation signals. This inverse regulation of IFNgamma- vs. E. coli-induced cytokine production by JAK inhibitors including Ruxolitinib was similarly observed for IL-6 and TNF-alpha production, but not for IL-10 production. Thus, JAK1 inhibition enhances IL-12p70 production in this context by increased DNA binding of CDK9. In contrast, weak RELA-activation signals (CD40L, LPS) depended on IFN-gamma induced STAT1/IRF1/IRF8 co-signalling, which was completely blocked by JAK inhibitors as reported before. Our results suggest a novel molecular mechanism of how cytokine responses to invading pathogens are separable from IFNgamma-dependent autoimmunity by targeting JAK1/STAT3 activation.
    Type of Publication: Journal article published
    PubMed ID: 25931145
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    Abstract: The intracellular transcription factor aryl hydrocarbon receptor (AHR) is bound and activated by xenobiotics, thereby promoting their catabolism by inducing expression of cytochrome P450 oxidase (CYP) genes through binding xenobiotic response elements (XRE) in their promoter region. In addition, it is involved in several cellular pathways like cell proliferation, differentiation, regeneration, tumor invasiveness and immune responses. Several pharmaceutical compounds like benzimidazoles activate the AHR and induce their own metabolic degradation. Using newly generated XRE-reporter mice, which allow in vivo bioluminescence imaging of AHR activation, we show here that the AHR is activated in vivo by teriflunomide (TER), which has recently been approved for the treatment of multiple sclerosis. While we did not find any evidence that the AHR mediates the immunomodulatory effects of TER, AHR activation led to metabolism and detoxification of teriflunomide, most likely via CYP. Mice deficient for the AHR show higher blood levels of teriflunomide, suffer from enhanced thrombo- and leukopenia and elevated liver enzymes as well as from severe gastrointestinal ulcers and bleeding which are lethal after 8-11 days of treatment. Leukopenia, acute liver damage and diarrhea have also been described as common side effects in human trials with TER. These data suggest that the AHR is relevant for detoxification not only of environmental toxins but also of drugs in clinical use, with potential implications for the application of AHR-modifying therapies in conjunction to TER in humans. The XRE-reporter mouse is a useful novel tool for monitoring AHR activation using in vivo imaging.
    Type of Publication: Journal article published
    PubMed ID: 26341389
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    Abstract: Disturbed redox homeostasis with both elevated reactive oxygen species (ROS) levels and antioxidant defense mechanisms has been reported in acute lymphoblastic leukemia (ALL). We therefore hypothesized that inhibition of pathways responsible for ROS detoxification renders ALL cells more susceptible for cell death. Here, we report that pharmacological inhibitors of key pathways for the elimination of ROS, i.e. Erastin, buthionine sulfoximine (BSO) and Auranofin, sensitize ALL cells for cell death upon treatment with the Smac mimetic LCL161 that antagonizes Inhibitor of Apoptosis (IAP) proteins. Erastin, BSO or Auranofin significantly increase LCL161-induced cell death and also act in concert with LCL161 to profoundly suppress long-term clonogenic survival in several ALL cell lines. Erastin or BSO cooperates with LCL161 to stimulate ROS production and lipid peroxidation prior to cell death. ROS production and lipid peroxidation are required for this cotreatment-induced cell death, since ROS scavengers or pharmacological inhibition of lipid peroxidation provides significant protection against cell death. These results emphasize that inhibition of antioxidant defense mechanisms can serve as a potent approach to prime ALL cells for LCL161-induced cell death.
    Type of Publication: Journal article published
    PubMed ID: 26774450
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Keywords: APOPTOSIS ; CANCER ; CELLS ; EXPRESSION ; GROWTH ; SURVIVAL ; tumor ; TUMOR-CELLS ; AGENTS ; Germany ; TOXICITY ; GENE ; LINES ; PATIENT ; DNA ; MECHANISM ; mechanisms ; VARIANTS ; CELL-SURVIVAL ; LESIONS ; ASSAY ; resistance ; INDUCED APOPTOSIS ; STRESS ; REPAIR ; chemotherapy ; leukemia ; LINE ; DAMAGE ; DNA-DAMAGE ; OXIDATIVE STRESS ; drug resistance ; DRUG-RESISTANCE ; DNA repair ; EXCISION-REPAIR ; DOUBLE-STRAND BREAKS ; traditional Chinese medicine ; LEUKEMIA-CELLS ; AGENT ; SINGLE ; molecular ; OXIDATIVE-STRESS ; ASSAYS ; DNA damage ; cancer chemotherapy ; DNA-POLYMERASE-BETA ; INDIVIDUAL CELLS ; natural compounds ; NORCANTHARIDIN
    Abstract: Cancer chemotherapy is often limited by patient's toxicity and tumor drug resistance indicating that new drug development and modification of existing drugs is critical for improving the therapeutic response. Traditional Chinese medicine is a rich source of potential anticancer agents. In particular, cantharidin (CAN), the active principle ingredient from the blister beetle, Mylabris, has anti-tumor activity, but the cytotoxic mechanism is unknown. In leukemia cells, cantharidin induces apoptosis by a p53-dependent mechanism. Cantharidin causes both DNA single- and double-strand breaks. Colony-forming assays with knockout and transfectant cells lines showed that DNA polymerase P, but not ERCC I, conferred increased cell survival after cantharidin treatment, indicating that base excision repair (BER), rather than nucleotide excision repair (NER), is important for CAN-induced DNA lesions. Oxidative stress-resistant thymic lymphoma-derived WEHI7.2 variants are also more resistant to cantharidin. These data suggest that cantharidin treatment causes oxidative stress that provokes DNA damage and p53-dependent apoptosis. (C) 2004 Elsevier Inc. All rights reserved
    Type of Publication: Journal article published
    PubMed ID: 15710358
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...