TY - JOUR A1 - Otto, Wolfgang A1 - Rubenwolf, Peter C. A1 - Burger, Maximilian A1 - Fritsche, Hans-Martin A1 - Rößler, Wolfgang A1 - May, Matthias A1 - Hartmann, Arndt A1 - Hofstädter, Ferdinand A1 - Wieland, Wolf F. A1 - Denzinger, Stefan T1 - Loss of aquaporin 3 protein expression constitutes an independent prognostic factor for progression-free survival: an immunohistochemical study on stage pT1 urothelial bladder cancer JF - BMC Cancer N2 - Background: Treatment of patients with stage pT1 urothelial bladder cancer (UBC) continues to be a challenge due to its unpredictable clinical course. Reliable molecular markers that help to determine appropriate individual treatment are still lacking. Loss of aquaporin (AQP) 3 protein expression has previously been shown in muscle-invasive UBC. The aim of the present study was to investigate the prognostic value of AQP3 protein expression with regard to the prognosis of stage pT1 UBC. Method: AQP 3 protein expression was investigated by immunohistochemistry in specimens of 87 stage T1 UBC patients, who were diagnosed by transurethral resection of the bladder (TURB) and subsequent second resection at a high-volume urological centre between 2002 and 2009. Patients underwent adjuvant instillation therapy with Bacillus Calmette-Guerin (BCG). Loss of AQP3 protein expression was defined as complete absence of the protein within the whole tumour. Expression status was correlated retrospectively with clinicopathological and follow-up data (median: 31 months). Multivariate Cox regression analysis was used to assess the value of AQP3 tumour expression with regard to recurrence-free (RFS), progression-free (PFS) and cancer-specific survival (CSS). RFS, PFS and CSS were calculated by Kaplan-Meier analysis and Log rank test. Results: 59% of patients were shown to exhibit AQP3-positive tumours, whereas 41% of tumours did not express the marker. Loss of AQP3 protein expression was associated with a statistically significantly worse PFS (20% vs. 72%, p=0.020). This finding was confirmed by multivariate Cox regression analysis (HR 7.58, CI 1.29 - 44.68; p=0.025). Conclusions: Loss of AQP3 protein expression in pT1 UBC appears to play a key role in disease progression and is associated with worse PFS. Considering its potential prognostic value, assessment of AQP3 protein expression could be used to help stratify the behavior of patients with pT1 UBC. KW - urothelial bladder carcinoma KW - progression KW - transitional cell carcinoma KW - bacillus calmette guerin KW - water channels KW - follow up KW - in vitro KW - recurrence KW - growth KW - T1 KW - tumor KW - proliferation KW - stage pT1 KW - aquaporin 3 protein KW - immunohistochemistry Y1 - 2012 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135679 VL - 12 IS - 459 ER - TY - JOUR A1 - Peindl, Matthias A1 - Göttlich, Claudia A1 - Crouch, Samantha A1 - Hoff, Niklas A1 - Lüttgens, Tamara A1 - Schmitt, Franziska A1 - Pereira, Jesús Guillermo Nieves A1 - May, Celina A1 - Schliermann, Anna A1 - Kronenthaler, Corinna A1 - Cheufou, Danjouma A1 - Reu-Hofer, Simone A1 - Rosenwald, Andreas A1 - Weigl, Elena A1 - Walles, Thorsten A1 - Schüler, Julia A1 - Dandekar, Thomas A1 - Nietzer, Sarah A1 - Dandekar, Gudrun T1 - EMT, stemness, and drug resistance in biological context: a 3D tumor tissue/in silico platform for analysis of combinatorial treatment in NSCLC with aggressive KRAS-biomarker signatures JF - Cancers N2 - Epithelial-to-mesenchymal transition (EMT) is discussed to be centrally involved in invasion, stemness, and drug resistance. Experimental models to evaluate this process in its biological complexity are limited. To shed light on EMT impact and test drug response more reliably, we use a lung tumor test system based on a decellularized intestinal matrix showing more in vivo-like proliferation levels and enhanced expression of clinical markers and carcinogenesis-related genes. In our models, we found evidence for a correlation of EMT with drug resistance in primary and secondary resistant cells harboring KRAS\(^{G12C}\) or EGFR mutations, which was simulated in silico based on an optimized signaling network topology. Notably, drug resistance did not correlate with EMT status in KRAS-mutated patient-derived xenograft (PDX) cell lines, and drug efficacy was not affected by EMT induction via TGF-β. To investigate further determinants of drug response, we tested several drugs in combination with a KRAS\(^{G12C}\) inhibitor in KRAS\(^{G12C}\) mutant HCC44 models, which, besides EMT, display mutations in P53, LKB1, KEAP1, and high c-MYC expression. We identified an aurora-kinase A (AURKA) inhibitor as the most promising candidate. In our network, AURKA is a centrally linked hub to EMT, proliferation, apoptosis, LKB1, and c-MYC. This exemplifies our systemic analysis approach for clinical translation of biomarker signatures. KW - EMT KW - drug resistance KW - invasion KW - stemness KW - 3D lung tumor tissue models KW - KRAS biomarker signatures KW - boolean in silico models KW - targeted combination therapy Y1 - 2022 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-270744 SN - 2072-6694 VL - 14 IS - 9 ER - TY - JOUR A1 - Suchotzki, Kristina A1 - May, Heidi A1 - Gamer, Matthias T1 - No effect of moderate alcohol intake on the detection of concealed identity information in the laboratory JF - Scientific Reports N2 - The Concealed Information Test (CIT) enables the detection of certain (e.g., crime-relevant or personal) information, even if participants aim to conceal their knowledge. The current preregistered study investigated whether previously observed impairing effects of alcohol intoxication on participants' performance in a reaction time CIT (RT CIT) field study also translate to a laboratory environment. In contrast to the previous study of Suchotzki and Gamer (Sci Rep 8:7825, 2018) in which alcohol consumption was voluntary and self-administered, the current study used a randomized assignment of participants to either an alcohol group (n=88; receiving a drink with 3 cl alcohol) or a sober control group (n=89; receiving a drink with just some alcohol drops to hide group assignment). After drink administration, participants completed an RT CIT, in which they were instructed to hide knowledge of their own identity. Blood alcohol concentration (BAC) was estimated via breath alcohol ratio. In contrast to the previous field study, results revealed no differences in CIT-performance between intoxicated and sober participants. Aside from questioning the robustness of the result of the previous field study, our results also point to a number of interesting theoretical explanations for the discrepancy between both results, which are elaborated in the discussion. KW - Concealed Information Test KW - concealed identity information KW - CIT Y1 - 2020 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-231208 VL - 10 ER - TY - JOUR A1 - Ullmann, Tobias A1 - Sauerbrey, Julia A1 - Hoffmeister, Dirk A1 - May, Simon Matthias A1 - Baumhauer, Roland A1 - Bubenzer, Olaf T1 - Assessing Spatiotemporal Variations of Sentinel-1 InSAR Coherence at Different Time Scales over the Atacama Desert (Chile) between 2015 and 2018 JF - Remote Sensing N2 - This study investigates synthetic aperture radar (SAR) time series of the Sentinel-1 mission acquired over the Atacama Desert, Chile, between March 2015 and December 2018. The contribution analyzes temporal and spatial variations of Sentinel-1 interferometric SAR (InSAR) coherence and exemplarily illustrates factors that are responsible for observed signal differences. The analyses are based on long temporal baselines (365–1090 days) and temporally dense time series constructed with short temporal baselines (12–24 days). Results are compared to multispectral data of Sentinel-2, morphometric features of the digital elevation model (DEM) TanDEM-X WorldDEM™, and to a detailed governmental geographic information system (GIS) dataset of the local hydrography. Sentinel-1 datasets are suited for generating extensive, nearly seamless InSAR coherence mosaics covering the entire Atacama Desert (>450 × 1100 km) at a spatial resolution of 20 × 20 meter per pixel. Temporal baselines over several years lead only to very minor decorrelation, indicating a very high signal stability of C-Band in this region, especially in the hyperarid uplands between the Coastal Cordillera and the Central Depression. Signal decorrelation was associated with certain types of surface cover (e.g., water or aeolian deposits) or with actual surface dynamics (e.g., anthropogenic disturbance (mining) or fluvial activity and overland flow). Strong rainfall events and fluvial activity in the periods 2015 to 2016 and 2017 to 2018 caused spatial patterns with significant signal decorrelation; observed linear coherence anomalies matched the reference channel network and indicated actual episodic and sporadic discharge events. In the period 2015–2016, area-wide loss of coherence appeared as strip-like patterns of more than 80 km length that matched the prevailing wind direction. These anomalies, and others observed in that period and in the period 2017–2018, were interpreted to be caused by overland flow of high magnitude, as their spatial location matched well with documented heavy rainfall events that showed cumulative precipitation amounts of more than 20 mm. KW - Chile KW - Atacama KW - Sentinel-1 KW - InSAR KW - coherence KW - geomorphology Y1 - 2019 U6 - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193836 SN - 2072-4292 VL - 11 IS - 24 ER -