Vocal Fold Fibroblasts in Reinke’s Edema Show Alterations Involved in Extracellular Matrix Production, Cytokine Response and Cell Cycle Control

The voice disorder Reinke’s edema (RE) is a smoking- and voice-abuse associated benign lesion of the vocal folds, defined by an edema of the Reinke’s space, accompanied by pathological microvasculature changes and immune cell infiltration. Vocal fold fibroblasts (VFF) are the main cell type of the lamina propria and play a key role in the disease progression. Current therapy is restricted to symptomatic treatment. Hence, there is an urgent need for a better understanding of the molecular causes of the disease. In the present study, we investigated differential expression profiles of RE and control VFF by means of RNA sequencing. In addition, fast gene set enrichment analysis (FGSEA) was performed in order to obtain involved biological processes, mRNA and protein levels of targets of interest were further evaluated. We identified 74 differentially regulated genes in total, 19 of which were upregulated and 55 downregulated. Differential expression analysis and FGSEA revealed upregulated genes and pathways involved in extracellular matrix (ECM) remodeling, inflammation and fibrosis. Downregulated genes and pathways were involved in ECM degradation, cell cycle control and proliferation. The current study addressed for the first time a direct comparison of VFF from RE to control and evaluated immediate functional consequences

Kapitel 10. Integrierte Perspektiven auf Strukturbedingungen

Strukturen wirken auf vielfältige Weise auf alltägliches Handeln und ihre adäquate Gestaltung ist daher notwendig, um klimafreundliches Verhalten dauerhaft zu ermöglichen. Die in Abschnitt 3 behandelten Strukturen fördern oder behindern eine Transformation in Richtung klimafreundli-chen Lebens maßgeblich und sind quer durch alle Handlungsfelder von Relevanz. Die einzelnen Strukturen, deren Analyse sich so weit möglich auf die besonderen Bedingungen in Österreich bezieht, thematisieren unterschiedliche Bereiche, die von Strukturveränderungen betroffen sind: Recht, Governance, Strukturen der öffentlichen Willensbildung in Diskursen und Medien sowie in Bildung und Wissensproduktion als auch wirtschaftliche Aktivitäten einschließlich ihrer tech-nischen Dimensionen und der zugehörigen Innovationssysteme. Ebenso werden Bereiche wie räumliche Ungleichheit und Raumplanung sowie soziale Sicherungssysteme in den Blick ge-nommen. Der Abschnitt betrachtet zudem die Versorgung mit Gütern und Dienstleitungen gene-rell, legt aber auch einen Akzent auf globalisierte Warenketten und Geld- und Finanzsysteme, um die interdependenten Strukturen über die Grenzen Österreichs hinaus zu thematisieren. Die strukturierende Rolle der gebauten Umwelt wird im abschließenden Kapitel zu netzgebundenen Infrastrukturen diskutiert

High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer

Abstract Background Breast cancer anti-estrogen resistance 1 (BCAR1/p130cas) is a hub for diverse oncogenic signaling cascades and promotes tumor development and progression. Methods To understand the effect of BCAR1 in prostate cancer, we analyzed its expression on more than 11,000 prostate cancer samples. BCAR1 expression levels were compared with clinical characteristics, PSA recurrence, molecular subtype defined by ERG status and 3p, 5q, 6q and PTEN deletion. Results BCAR1 staining was barely detectable in normal prostate glands but seen in 77.6% of 9472 interpretable cancers, including strong expression in 38.5%, moderate in 23.2% and weak in 15.9% of cases. BCAR1 up regulation was associated with positive ERG status (p < 0.0001), high Gleason score (p < 0.0001), advanced pathological tumor stage (p = 0.0082), lower preoperative PSA level (p < 0.0001), increased cell proliferation (p < 0.0001), early PSA recurrence (p = 0.0008), and predicted prognosis independently from clinico-pathological parameters available at the time of the initial biopsy. However, subset analyses revealed that the prognostic impact of BCAR1 expression was limited to ERG-negative cancer. That BCAR1 up regulation was linked to almost all analyzed deletions (p < 0.0001 each for PTEN, 5q, 6q deletion) may suggest a functional link to genomic instability. Conclusion The results of our study identify BCAR1 as a prognostic biomarker with potential clinical value for risk stratification of ERG-negative prostate cancer

Kapitel I: Zusammenfassung Für Entscheidungstragende

Derzeit ist es schwierig, in Österreich klimafreundlich zu leben. In den meisten Lebensbereichen, von Arbeit über Mobilität und Wohnen bis hin zu Ernährung und Freizeitgestaltung, fördern bestehende Strukturen klimaschädigendes Verhalten und erschweren klimafreundliches Leben (hohe Übereinstimmung, starke Literaturbasis). {Kap 3-9} Der vorliegende Bericht bestärkt somit für Österreich die Aussagen des Klimarates der Vereinten Nationen (Intergovernmental Panel on Climate Change, IPCC), wonach zur Erreichung der Ziele des Pariser Klimaabkommens grundlegende Transformationen im Sinne umfassender Strukturveränderungen notwendig sind (hohe Übereinstimmung, starke Literaturbasis)

Kapitel IV: Technical Summary

This technical summary provides an overview of the main statements of the APCC SR Structures for Climate-Friendly Living chapters. Based on scientific literature, the report assesses different approaches for transforming structures in order to make climate-friendly living in Austria possible and make it permanently and quickly the new status quo

Kapitel II: Summary for Policymakers

This technical summary provides an overview of the main statements of the APCC SR Structures for Climate-Friendly Living chapters. Based on scientific literature, the report assesses different approaches for transforming structures in order to make climate-friendly living in Austria possible and make it permanently and quickly the new status quo

Additional file 1: of High BCAR1 expression is associated with early PSA recurrence in ERG negative prostate cancer

Figure S1. Kaplan-Meier plots of prostate specific antigen (PSA) recurrence after radical prostatectomy and negative or strong BCAR1 staining in subsets of all cancers defined by (a) classical Gleason score, (b-h) quantitative Gleason score defined by the percentage of Gleason 4 grade and (i-j) by the tertiary Gleason 5 grade. Figure S2. Kaplan-Meier plots of prostate specific antigen (PSA) recurrence after radical prostatectomy and BCAR1 staining in subsets of ERG negative cancers defined by (a) classical and (b-h) quantitative Gleason score, defined by the percentage of Gleason 4 grade and (i-j) by the tertiary Gleason 5 grade. Figure S3. Correlation of BCAR1 staining and androgen receptor (AR) staining in all cancers, Figure S4. Kaplan-Meier plot of prostate specific antigen (PSA) recurrence after radical prostatectomy and clinical stage in all cancers, Figure S5. Kaplan-Meier plot of prostate specific antigen (PSA) recurrence after radical prostatectomy and Gleason score at biopsy in all cancers, Table S1. Pathological and clinical data of the arrayed prostate cancer, Table S2. Association between BCAR1 staining and prostate cancer clinical characteristics in ERG–fusion negative and positive subsets, Table S3. Association between BCRA1 expression and Ki67-labeling index depending on ERG-fusion status in different Gleason scores. (DOC 5580 kb

Integrative genomic analyses reveal an androgen-driven somatic alteration landscape in early-onset prostate cancer

SummaryEarly-onset prostate cancer (EO-PCA) represents the earliest clinical manifestation of prostate cancer. To compare the genomic alteration landscapes of EO-PCA with “classical” (elderly-onset) PCA, we performed deep sequencing-based genomics analyses in 11 tumors diagnosed at young age, and pursued comparative assessments with seven elderly-onset PCA genomes. Remarkable age-related differences in structural rearrangement (SR) formation became evident, suggesting distinct disease pathomechanisms. Whereas EO-PCAs harbored a prevalence of balanced SRs, with a specific abundance of androgen-regulated ETS gene fusions including TMPRSS2:ERG, elderly-onset PCAs displayed primarily non-androgen-associated SRs. Data from a validation cohort of > 10,000 patients showed age-dependent androgen receptor levels and a prevalence of SRs affecting androgen-regulated genes, further substantiating the activity of a characteristic “androgen-type” pathomechanism in EO-PCA