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Additional file 1: Figure S1. HMOX1 and GTSF1 are differentially expressed upon KPNA2 depletion. HLE cells were siRNA-treated and harvested 72 h later. Lysates were immunoblotted using the indicated antibodies. Figure S2. KPNA2 depletion reduces the clonogenic capacity of HCC cells being phenocopied by stathmin knockdown. a HLE and HLF cells were treated with ctrl. or stathmin siRNAs and harvested 72 h later. Lysates were immunoblotted using the indicated antibodies. (b,c) HLF cells were treated either with ctrl. or pooled KPNA2 siRNAs (siRNAs KPNA2#1 and #2) and colony formation was analyzed 14 days after treatment by crystal violet staining (n = 4; p

Additional file 2: Table S1. Significantly differentially expressed proteins upon KPNA2-depletion. List of proteins with a log2 fold change of ≥ 0.8 or ≤ − 0.8 and an individual p-value of ≤ 0.01 that were differentially expressed following KPNA2 depletion as indicated by LC-MS/MS analysis. (DOCX 14 kb)

Additional file 3: Table S2. Differentially expressed proteins upon KPNA2-depletion. List of all proteins that were quantified in the LC-MS/MS approach following KPNA2 depletion. (DOCX 122 kb)

Figure S1. (A) Heatmap showing genes that displayed discordant NMR vs. GP fold changes at the transcript and protein level. Only cases significant in both comparisons (q

Figure S4. SULT1C2 decreases with aging in NMR. Related to Fig. 5. (PDF 328 kb)

Figure S3. Examples of enzymes involved in fatty acid beta-oxidation and xenobiotic metabolism that decrease during aging in human liver. (A) Additional examples of enzymes involved in lipid metabolism decreasing during aging in human liver. (B) Detoxifying enzymes decreasing during aging in both NMR and humans. Only significantly affected genes are shown; cut offs: NMR aging, combined qâ

Figure S2. Comparison of liver proteomes between middle-aged and young NMRs, and correlation analysis of transcript level differences in NMR vs. GP and NMR aging. (A) Representative micrographs show H&E stained (FFPE) liver tissue sections from NMRs of the indicated age groups. Scale bar = 100 μm. (B) Livers from 4 young (1 yo) and 4 middle-aged (> 10 yo) NMRs were compared by Tandem Mass Tags (TMT) based quantitative mass spectrometry. Hierarchical clustering based on the correlation between proteome profiles based on 4936 protein groups cross-quantified between the two age groups (Additional file 5: Table S4). (C) Comparison of protein fold changes calculated between old vs. young (x-axis) and middle-aged vs. young (y-axis) NMRs. Colored dots indicate proteins significant (q

Arbeit an der Bibliothek noch nicht eingelangt - Daten nicht geprüft Abweichender Titel laut Übersetzung des Verfassers/der Verfasserin Karl-Franzens-Universität Graz, Univ., Masterarbeit, 2016

In der vorliegenden Arbeit wurden die Proteinexpressionen von P53, P63, Hdm2, P14ARF und P16INK4a eines Tissue-Mikroarray (TMA) von invasiven Harnblasenkarzinomen digitalisiert und auf das phänotypische Markerprofil hin untersucht. P53, P14ARF und Hdm2 sind zentraler Bestandteil des Regulationsmechanismus, der in gesunden Zellen zum Zellzyklusarrest führt, in Tumorzellen jedoch oft mutiert ist und die betroffenen Zellen immortalisieren kann und deren Progression ermöglicht[133, 224, 222]. Die Gruppe von Karni-Schmidt et al. [114] hat herausgefunden, dass ΔNP63-positive Harnblasenkarzinome eine besonders schlechte Prognose aufweisen. Außerdem konnten die Ergebnisse von Choi et al. [34] der epithelialen-mesenschymalen Transition eine bedeutende Rolle in der Entstehung des Harnblasenkarzinoms zuschreiben. Häufig auftretende Mutationen im invasiven Blasenkarzinom sind Veränderungen des INK4a/ARF-Genlokus, der für die Proteine P14ARF und P16INK4a kodiert [136]. Die vorliegende Arbeit beschäftigt sich daher auch mit der Frage des Zusammenhangs der Regulation der beiden Proteine. Die rasanten Entwicklungen neuer technischer Apparate zur Digitalisierung und Verbreitung eingescannter histologischer Präparate haben starken Einfluss auf die Integration der Telemedizin in die Routine pathologischer Begutachtungen. So kann in Ländern mit großer geographischer Fläche oder nicht ausreichendem Ärztebestand die Patientenversorgung deutlich verbessert werden, wie die positiven Ergebnisse aus Kanada und Ägypten belegen [7, 8, 243]. Ob diese Verfahren auch geeignet sind, die in der experimentellen Forschung etablierten Aufbereitungs- und Nachweistechniken im Rahmen der Untersuchung von Markerprofilen an Tumorproben abzubilden, war weiterer Gegenstand der vorliegenden Arbeit. In this thesis the protein expression profiles of P53, P63, Hdm2, P14ARF and P16INK4a on a tissue microarray (TMA) from invasive bladder cancer were digitalized and their phenotypic expression-pattern was investigated. P53, P14ARF and Hdm2 are part of the regulatory mechanism which plays a vital role in cell cycle arrest in healthy cells. However, mutation often occurs in tumour cells leading to immortalization and progression [133, 224, 222]. Karni-Schmidt et al. [114] discovered that ΔNP63 positive bladder carcinomas hold an especially poor prognosis. Additionally, Choi et al. [34] were able to demonstrate the important role of epithelial-mesenchymal transition in the development of invasive bladder cancer. Common alterations seen in invasive bladder carcinomas are mutations of the INK4a/ARF gene locus, which codes for P14ARF and P16INK4a [136]. Thus, the present thesis implemented discussions on the correlation of the regulation of these two proteins. The fast development of new technical devices to digitalize and share scanned histologic slides had a strong impact of the integration of telemedicine in routine use as a tool for histopathologic evaluation. With that patient care could be improved in countries covering an extensive surface and countries suffering from a shortage of medical personnel as positive results in Canada and Egypt are demonstrating [7, 8, 243]. To investigate, if these measures are also suitable to be implemented in addition to the established techniques for the preparation and analyses as part of the investigation of marker profiles of tumour samples, was an additional part of the provided work.