Your email was sent successfully. Check your inbox.

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

Proceed reservation?

Export
  • 1
    Keywords: EXPRESSION ; RISK ; COMPLEXES ; AMPLIFICATION ; OVARIAN-CANCER ; MUTATIONS ; VARIANT ; GENOME-WIDE ASSOCIATION ; GENETIC-VARIATION ; CONFERS SUSCEPTIBILITY
    Abstract: A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell-cycle protein. We performed genetic fine-mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r(2) 〉/= 0.7) associated with increased bladder cancer risk. From this group, we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWASs, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele OR = 1.18 [95% confidence interval (CI), 1.09-1.27, P = 4.67 x 10(-5)] versus OR = 1.01 (95% CI, 0.93-1.10, P = 0.79) for nonaggressive disease, with P = 0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (P = 0.013) and, independently, with each rs7257330-A risk allele (Ptrend = 0.024). Overexpression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E overexpression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. Cancer Res; 74(20); 5808-18. (c)2014 AACR.
    Type of Publication: Journal article published
    PubMed ID: 25320178
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Abstract: Constitutive activation of the antiapoptotic nuclear factor-kappaB (NF-kappaB) signaling pathway is a hallmark of the activated B-cell-like (ABC) subtype of diffuse large B-cell lymphomas (DLBCL). Recurrent oncogenic mutations are found in the scaffold protein CARMA1 (CARD11) that connects B-cell receptor (BCR) signaling to the canonical NF-kappaB pathway. We asked how far additional downstream processes are activated and contribute to the oncogenic potential of DLBCL-derived CARMA1 mutants. To this end, we expressed oncogenic CARMA1 in the NF-kappaB negative DLBCL lymphoma cell line BJAB. By a proteomic approach we identified recruitment of beta-catenin and its destruction complex consisting of APC, AXIN1, CK1alpha and GSK3beta to oncogenic CARMA1. Recruitment of the beta-catenin destruction complex was independent of CARMA1-BCL10-MALT1 complex formation or constitutive NF-kappaB activation and promoted the stabilization of beta-catenin. The beta-catenin destruction complex was also recruited to CARMA1 in ABC DLBCL cell lines, which coincided with elevated beta-catenin expression. In line, beta-catenin was frequently detected in non-GCB DLBCL biopsies that rely on chronic BCR signaling. Increased beta-catenin amounts alone were not sufficient to induce classical WNT target gene signatures, but could augment TCF/LEF-dependent transcriptional activation in response to WNT signaling. In conjunction with NF-kappaB, beta-catenin enhanced expression of immunosuppressive interleukin-10 and suppressed antitumoral CCL3, indicating that beta-catenin can induce a favorable tumor microenvironment. Thus, parallel activation of NF-kappaB and beta-catenin signaling by gain-of-function mutations in CARMA1 augments WNT stimulation and is required for regulating the expression of distinct NF-kappaB target genes to trigger cell-intrinsic and extrinsic processes that promote DLBCL lymphomagenesis.
    Type of Publication: Journal article published
    PubMed ID: 26776161
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: EXPRESSION ; SYSTEM ; GENOME ; NF-KAPPA-B ; ACTIVATION ; INDUCTION ; T-CELLS ; GENE-REGULATION ; STERNBERG CELLS ; FACTOR-BINDING
    Abstract: Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-kappaB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.
    Type of Publication: Journal article published
    PubMed ID: 25288773
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 0375-9601
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Physics
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-1173
    Keywords: Schlüsselwörter Vernarbendes Pemphigoid ; Epiligrin-Autoantikörper ; Immunsuppressive Therapie ; Paraneoplasie ; Key words Cicatricial pemphigoid ; Anti-epiligrin autoantibodies ; Immunosuppressive therapy ; Paraneoplasia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Summary A 71 year old female patient presented with erosions of the oral, genital and ocular mucosa, but without skin lesions. One year prior to the onset of lesions, a metastatic adenocarcinoma of the endometrium had been diagnosed. In perilesional skin, direct immunofluorescence showed linear deposits of C3 and IgG along the basement membrane zone. Indirect immunofluorescence demonstrated anti-basement membrane zone antibodies which bound exclusively to the dermal side of 1M NaCl-split skin. In immunoprecipitation studies, the autoantibodies bound a set of proteins characteristic of epiligrin/laminin-5, and they specifically immunoblotted the alpha-subunit of this protein. These results confirmed our presumed diagnosis of anti-epiligrin cicatricial pemphigoid. Combined treatment with methylprednisolone and dapsone resulted in prompt remission, despite progression of her malignancy. So far, only eight patients with anti-epiligrin cicatricial pemphigoid have been reported worldwide. Our patient represents the first case from Austria and is clinically and immunopathologically similar to previously reported cases.
    Notes: Zusammenfassung Berichtet wird über eine 71jährige Patientin mit erosiver Stomatitis, Vulvitis und Konjunktivitis, jedoch ohne Hautbeteiligung, bei der ein Jahr vor dem Auftreten der Schleimhautläsionen ein metastasierendes Adenokarzinom des Endometriums diagnostiziert worden war. Die Histologie zeigte eine junktionale Spaltbildung, die direkte Immunfluoreszenz periläsionaler Haut lineare Ablagerungen von C3 und IgG entlang der BMZ. Mit Hilfe der indirekten Immunfluoreszenz ließen sich niedrigtitrige anti-BMZ-Antikörper nachweisen, die in der Spalthautanalyse am Boden der artifiziellen Blase banden. Die Autoantikörper der Patientin präzipitierten ein Spektrum an Proteinen, das für Epiligrin/Laminin-5 typisch ist, und banden im Immunoblot spezifisch die alpha-Kette des Heteropeptids. Aufgrund dieser Ergebnisse stellten wir die Diagnose eines vernarbenden Pemphigoids vom anti-Epiligrin-Typ. Unter Behandlung mit Methylprednisolon und Dapson konnte eine rasche Remission erzielt werden, trotz Progression des metastasierenden Adenokarzinoms. Bisher wurden weltweit nur 8 Patienten mit vernarbendem Pemphigoid vom anti-Epiligrin-Typ beschrieben; unsere Patientin stellt den ersten in Österreich diagnostizierten Fall dar und gleicht sowohl klinisch als auch immunpathologisch den bisher beschriebenen Fällen.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1365-2842
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Medicine
    Notes: Summary  Mismatch occurring during the fabrication of implant-supported dentures may induce stress to the peri-implant bone. The purpose of this study was to investigate the influence of two different alloys and the fabrication method on the marginal accuracy of cast partial dentures. Two laboratory implants were bonded into an aluminium block so that the distance between their longitudinal axes was 21 mm. Frameworks designed for screw-retained partial dentures were cast either with pure titanium (rematitan) or with a CoCr-alloy (remanium CD). Two groups of 10 frameworks were cast in a single piece. The first group was made of pure titanium, and the second group of a CoCr-alloy (remanium CD). A third group of 10 was cast in two pieces and then laser-welded onto a soldering model. This latter group was also made of the CoCr-alloy. All the frameworks were screwed to the original model with defined torque. Using light microscopy, marginal accuracy was determined by measuring vertical gaps at eight defined points around each implant. Titanium frameworks cast in a single piece demonstrated mean vertical gaps of 40 μm (s.d. = 11 μm) compared with 72 μm (s.d. = 40 μm) for CoCr-frameworks. These differences were not significant (U-test, P = 0·124) because of a considerable variation of the values for CoCr-frameworks (minimum: 8 μm and maximum: 216 μm). However, frameworks cast in two pieces and mated with a laser showed significantly better accuracy in comparison with the other experimental groups (mean: 17 μm ± 6; P 〈 0·01). (i) The fit of implant-supported partial dentures cast with pure titanium in a single piece is preferable to that of those made with the CoCr-alloy and (ii) the highest accuracy can be achieved by using a two-piece casting technique combined with laser welding. Manufacturing the framework pieces separately and then welding them together provides the best marginal fit.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1292-895X
    Keywords: PACS. 68.45.Gd Wetting - 68.10.Cr Surface energy (surface tension, interface tension, angle of contact, etc.) - 47.20.Dr Surface-tension-driven instability
    Source: Springer Online Journal Archives 1860-2000
    Topics: Physics
    Notes: Abstract: Wetting of structured or imprinted surfaces which leads to a variety of different morphologies such as droplets, channels or thin films is studied theoretically using the general framework of surface or interface thermodynamics. The first variation of the interfacial free energy leads to the well-known Laplace equation and a generalized Young equation which involves spatially dependent interfacial tensions. Furthermore, we perform the second variation of the free energy for arbitrary surface patterns and arbitrary shape of the wetting morphology in order to derive a new and general stability criterion. The latter criterion is then applied to cylindrical segments or channels on homogeneous and structured surfaces.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 8
    ISSN: 0020-7373
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Computer Science
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 9
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Journal of Electroanalytical Chemistry 353 (1993), S. 131-145 
    ISSN: 0022-0728
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Chemistry and Pharmacology
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
  • 10
    ISSN: 1432-1351
    Keywords: Key words Crustacean ; Sensorimotor ; Ultrastructure ; Multilamellar sheath ; Myelinated axons
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract Speed of nerve impulse conduction is greatly increased by myelin, a multi-layered membranous sheath surrounding axons. Myelinated axons are ubiquitous among the vertebrates, but relatively rare among invertebrates. Electron microscopy of calanoid copepods using rapid cryofixation techniques revealed the widespread presence of myelinated axons. Myelin sheaths of up to 60 layers were found around both sensory and motor axons of the first antenna and interneurons of the ventral nerve cord. Except at nodes, individual lamellae appeared to be continuous and circular, without seams, as opposed to the spiral structure of vertebrate and annelid myelin. The highly organized myelin was characterized by the complete exclusion of cytoplasm from the intracellular spaces of the cell generating it. In regions of compaction, extracytoplasmic space was also eliminated. Focal or fenestration nodes, rather than circumferential ones, were locally common. Myelin lamellae terminated in stepwise fashion at these nodes, appearing to fuse with the axolemma or adjacent myelin lamellae. As with vertebrate myelin, copepod sheaths are designed to minimize both resistive and capacitive current flow through the internodal membrane, greatly speeding nerve impulse conduction. Copepod myelin differs from that of any other group described, while sharing features of every group.
    Type of Medium: Electronic Resource
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...