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Die vorliegende Arbeit befasst sich mit der Rolle von humanen Perizyten für die neurale Invasion und Angiogenese im duktalen Adenokarzinom des Pankreas (PDAC). Es zeigte sich, dass insbesondere CD146+Perizyten im PDAC ausgeprägter vorkommen als im gesunden Pankreasgewebe. In vitro weisen pankreaskarzinomzell-aktivierte Perizyten eine veränderte Zellmorphologie auf, sowie ein verändertes Genexpressionsprofil. Die Ergebnisse der vorliegenden Arbeit deuten daraufhin, dass eine Aktivierung von Perizyten in der Tumormikroumgebung des PDAC stattfindet. Pancreatic ductal adenocancinoma (PDAC) exhibits an overproportional degree of neural invasion (NI). Here, we investigated the role of human pericytes in PDAC-associated NI and angiogenesis. We found that CD146+pericytes were increased around microcapillaries when compared to normal pancreas. Upon co-culture with PDAC cells, pericytes show altered cell morphology with increased cell surface area and increased gene expression of pro-inflammatory and metabolic pathways. This indicates that there might be an activation of pericytes in the tumor microenvironment of human PDAC.

Objectives and Background: Congenital malformations of the kidney and urinary tract (CAKUT) have a prevalence of 4-60 in 10,000livebirths and constitute for 40-50% of all end stage pediatric kidney disease. CAKUT can have a genetic background due to monogenetic inherited disease such as PKD or ciliopathies. They can also be found in combination with extra-renal findings as part of a syndrome. Upon detection of genitourinary malformations during the fetal anomaly scan the question arises if further genetic testing is required. The purpose of this study was to determine the phenotypic presentation of CAKUT cases and the results of exome analysis (WES). Methods: This is a retrospective analysis of 63 fetal cases with a diagnosis of CAKUT or DSD at a single center between August 2018 and December 2022. Results: A total of 63 cases (5.6%) out of 1123 matched CAKUT phenotypes including renal parenchyma malformations. In 15out of 63WES analysis a pathogenic variant was detected (23.8%). In fetuses with isolated CAKUT the rate of detecting a pathogenic variant on exome sequencing was five out of 44 (11.4%). Ten out of 19 fetuses (52.6%) that displayed extra-renal findings in combination with CAKUT were diagnosed with a pathogenic variant. Conclusion: WES provides an increase in diagnosing pathogenic variants in cases of prenatally detected CAKUT. Especially in fetuses with extra-renal malformations, WES facilitates a gain in information on the fetal genotype to enhance prenatal counselling and management.