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  • 1
    Keywords: CELLS ; EXPRESSION ; IN-VIVO ; resistance ; SINGLE NUCLEOTIDE POLYMORPHISMS ; CIRCULATING LEVELS ; GENETIC-VARIATION ; QUANTITATIVE PCR ; IGFBP-3 POLYMORPHISMS ; PATHWAY GENES
    Abstract: Intrinsic and acquired resistance to the monoclonal antibody drug trastuzumab is a major problem in the treatment of HER2-positive breast cancer. A deeper understanding of the underlying mechanisms could help to develop new agents. Our intention was to detect genes and single nucleotide polymorphisms (SNPs) affecting trastuzumab efficiency in cell culture. Three HER2-positive breast cancer cell lines with different resistance phenotypes were analyzed. We chose BT474 as model of trastuzumab sensitivity, HCC1954 as model of intrinsic resistance, and BTR50, derived from BT474, as model of acquired resistance. Based on RNA-Seq data, we performed differential expression analyses on these cell lines with and without trastuzumab treatment. Differentially expressed genes between the resistant cell lines and BT474 are expected to contribute to resistance. Differentially expressed genes between untreated and trastuzumab treated BT474 are expected to contribute to drug efficacy. To exclude false positives from the candidate gene set, we removed genes that were also differentially expressed between untreated and trastuzumab treated BTR50. We further searched for SNPs in the untreated cell lines which could contribute to trastuzumab resistance. The analysis resulted in 54 differentially expressed candidate genes that might be connected to trastuzumab efficiency. 90% of 40 selected candidates were validated by RT-qPCR. ALPP, CALCOCO1, CAV1, CYP1A2 and IGFBP3 were significantly higher expressed in the trastuzumab treated than in the untreated BT474 cell line. GDF15, IL8, LCN2, PTGS2 and 20 other genes were significantly higher expressed in HCC1954 than in BT474, while NCAM2, COLEC12, AFF3, TFF3, NRCAM, GREB1 and TFF1 were significantly lower expressed. Additionally, we inferred SNPs in HCC1954 for CAV1, PTGS2, IL8 and IGFBP3. The latter also had a variation in BTR50. 20% of the validated subset have already been mentioned in literature. For half of them we called and analyzed SNPs. These results contribute to a better understanding of trastuzumab action and resistance mechanisms.
    Type of Publication: Journal article published
    PubMed ID: 25710561
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  • 2
    ISSN: 1437-1596
    Keywords: Livor mortis ; Blanching ; Colorimetry ; Measurement of pressure ; Estimation of time of death ; Totenflecke, Wegdrückbarkeit ; Totenflecke, Farbmessung ; Totenflecke, Druckmessung ; Todeszeitschätzung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine , Law
    Description / Table of Contents: Zusammenfassung Bislang wurde die „Wegdrückbarkeit” der Totenflecken bei der Todeszeitschätzung im wesentlichen nach subjektiven Eindrücken beurteilt-danach, ob die Totenflecke leicht, vollständig, schwer und/oder unvollständig wegdrückbar sind. Ein neues Meßsystem objektiviert die Beziehungen zwischen Kraftaufwand und Farbänderung der livores („Wegdrückbarkeit”) durch digitale Verarbeitung von Meßgrößen. Der Kraftaufwand während des Drucks auf den Totenfleck wird mittels Dehnungsmeßstreifen elektronisch erfaßt. Bei Erreichen definierter Druckstärken (10, 20, 30 bis 100 Newton) löst ein Computerprogramm jeweils eine Farbmessung mit einem handelsüblichen Farbdifferenz-Meßgerät aus. Die Farbmetrik arbeitet nach dem Dreibereichsverfahren. Alle Parameter werden ineinem Meßvorgang erfaßt und über einen Meßkonverter in einen Computer eingelesen. Die Darstellung des Farborts erfolgt im L,a b-System (CIELAB nach DIN 5033, DIN 6174), das der Physiologie des Sehens sehr nahekommt. Außerdem können Farbveränderungen über eine Farbabstandsformel (ΔE) weitgehend unabhängig vom Grundton der Haut analysiert werden. In ersten Ergebnissen von Messungen an Leichen zeigen sich regelhafte postmortale Abläufe der Farbveränderungen von Totenflekken bei zunehmender Druckstärke.
    Notes: Summary Until now, blanching of livor mortis in estimating time of death has generally been assessed based on subjective impressions, i.e. on whether blanching is visible after the application of pressure. We have developed a measuring system that uses digital processing to objectify the relationship between the pressure applied and blanching of postmortem lividity. The pressure is electronically registered by a strain gauge. At predefined levels (10, 20, 30, up to 100N) the software triggers a color measurement by a commerically available tristimulus colorimeter. All parameters are measured in a single procedure and routed to the computer through a data interface. The pressure-induced color changes in the livor mortis are evaluated according to the L*, a*, b* system (CIE-LAB according to DIN 5033, DIN 6174), which closely approximates the physiology of sight. An additional color spacing formula (AE) allows analysis of color changes irrespective of the basic skin tone. Initial measurements on cadavers showed that application of increasing pressure produced regular courses of color changes in livor mortis.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1435-2451
    Keywords: Cementless hip prostheses ; Circumferential stress ; Zementfreie Hüftendoprothesen ; Vorspannung
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Description / Table of Contents: Zusammenfassung In einer von der DFG unterstützten experimentellen Untersuchung wurde die Vorlast am proximalen Femur nach Implantation verschiedener zementfreier Hüftendoprothesen gemessen. Als Prüfkörper diente ein sogenannter „Kunststoffnormfemur”. Zuvor waren mit Hilfe der Spannungsoptik die optimalen Applikationspunkte für Dehnungsmessstreifen ermittelt worden. Von den 6 bisher untersuchten Prothesen hatten die PM-Prothese, die bitrochantere Prothese und die Rippensystem-Prothese die höchste Vorlast. Bei der MR-Prothese und der Müller Geradschaftprothese fiel eine gegensinnige Vorspannung auf, während die isoelastische Prothese nur eine geringe Vorlast erzeugte.
    Notes: Summary In an experimental study supported by the German Research Society (DFG), the stress at the proximal femur was measured after implantation of different cementless hip prostheses. As a model, we used an artificial femur called the “Kunststoffnormfemur.” Previously, the optimal points for the application of strain gauges had been found with the aid of photo stress. Of the six prostheses, tested so far, the PM Prosthesis, the Bitrochantere Prosthesis and the Rippensystem Prosthesis showed the greatest circumferential stress. Using the MR Prosthesis and the Müller Geradschaftprosthesis, inverse stress could be measured; the Isoelastische Prosthesis revealed only a small amount of stress.
    Type of Medium: Electronic Resource
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