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  • 1
    In: Neuroendocrinology, S. Karger AG, Vol. 104, No. 3 ( 2017), p. 302-312
    Abstract: 〈 b 〉 〈 i 〉 Background/Aims: 〈 /i 〉 〈 /b 〉 Neuroendocrine tumors of the small intestine (SI-NETs) exhibit an increasing incidence and high mortality rate. Until now, no fundamental molecular event has been linked to the tumorigenesis and progression of these tumors. Only the loss of chromosome 18 (Chr18) has been shown in up to two thirds of SI-NETs, whereby the significance of this alteration is still not understood. We therefore performed the first comprehensive study to identify Chr18-related events at the genetic, epigenetic and gene/protein expression levels. 〈 b 〉 〈 i 〉 Methods: 〈 /i 〉 〈 /b 〉 We did expression analysis of all seven putative Chr18-related tumor suppressors by quantitative real-time PCR (qRT-PCR), Western blot and immunohistochemistry. Next-generation exome sequencing and SNP array analysis were performed with five SI-NETs with (partial) loss of Chr18. Finally, we analyzed all microRNAs (miRNAs) located on Chr18 by qRT-PCR, comparing Chr18+/- and Chr18+/+ SI-NETs. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 Only DCC (deleted in colorectal cancer) revealed loss of/greatly reduced expression in 6/21 cases (29%). No relevant loss of SMAD2, SMAD4, elongin A3 and CABLES was detected. PMAIP1 and maspin were absent at the protein level. Next-generation sequencing did not reveal relevant recurrent somatic mutations on Chr18 either in an exploratory cohort of five SI-NETs, or in a validation cohort (n = 30). SNP array analysis showed no additional losses. The quantitative analysis of all 27 Chr18-related miRNAs revealed no difference in expression between Chr18+/- and Chr18+/+ SI-NETs. 〈 b 〉 〈 i 〉 Conclusion: 〈 /i 〉 〈 /b 〉 DCC seems to be the only Chr18-related tumor suppressor affected by the monoallelic loss of Chr18 resulting in a loss of DCC protein expression in one third of SI-NETs. No additional genetic or epigenetic alterations were present on Chr18.
    Type of Medium: Online Resource
    ISSN: 0028-3835 , 1423-0194
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2017
    detail.hit.zdb_id: 1483028-0
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  • 2
    In: Psychopathology, S. Karger AG, Vol. 46, No. 1 ( 2013), p. 34-44
    Abstract: 〈 b 〉 〈 i 〉 Background: 〈 /i 〉 〈 /b 〉 One widespread view holds that vulnerability to major depressive disorder (MDD) is linked to overall increases in negative emotionality. In contrast, cognitive attribution theories emphasize the importance of blaming oneself rather than others for negative events. Thus far, the contrasting predictions of these models have not been directly compared. Following the attributional perspective, we tested the hypothesis that people with remitted MDD show no overall bias towards negative emotions, but a selective bias towards self-blaming emotions relative to those emotions associated with blaming others. 〈 b 〉 〈 i 〉 Sampling and Methods: 〈 /i 〉 〈 /b 〉 We compared a remitted MDD and a control group on a novel experimental test that allowed us to directly compare proneness to specific emotions associated with different types of self-blame (guilt, shame, self-contempt/disgust) and blame of others (other-indignation/anger, other-contempt/disgust) whilst controlling for negative valence and medication status, and excluding comorbidity. 〈 b 〉 〈 i 〉 Results: 〈 /i 〉 〈 /b 〉 In agreement with our hypothesis, individuals with remitted MDD exhibited an increased self-contempt bias (difference between contempt/disgust towards self and others) but no increased proneness to any other negative emotion or overall increases in perceived negative valence of stimuli. Moreover, the remitted MDD group exhibited reduced contempt/disgust towards others. 〈 b 〉 〈 i 〉 Conclusions: 〈 /i 〉 〈 /b 〉 Our results corroborate the prediction that vulnerability to MDD is associated with an imbalance of specific self- and other-blaming emotions rather than a general increase in negative emotions. Based on the composition of our sample, we speculate that self-contempt bias may be particularly characteristic of melancholic MDD subtypes and could be useful for stratification of depression in the future.
    Type of Medium: Online Resource
    ISSN: 0254-4962 , 1423-033X
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2013
    detail.hit.zdb_id: 1483565-4
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  • 3
    In: Digestion, S. Karger AG, Vol. 60, No. 6 ( 1999), p. 544-548
    Abstract: 〈 i 〉 Background/Aim: 〈 /i 〉 Mutations of the adenomatous polyposis coli (APC) tumor suppressor gene have been described in a subset of pancreatic carcinomas. The APC gene modulates the β-catenin-Tcf pathway. The major player in this pathway is the β-catenin protein encoded by the 〈 i 〉 β 〈 /i 〉 -catenin gene. A variety of different tumors, including colon, prostate, endometrial, and hepatocellular carcinomas, carry mutations in exon 3 of the 〈 i 〉 β 〈 /i 〉 -catenin gene. The aim of this study was to determine the role of the 〈 i 〉 β 〈 /i 〉 -catenin gene in the genesis of exocrine and endocrine tumors of the pancreas. 〈 i 〉 Methods: 〈 /i 〉 78 ductal pancreatic adenocarcinomas, 14 ductal pancreatic cancer cell lines, and 33 endocrine pancreatic tumors were evaluated for mutations in exon 3 of the 〈 i 〉 β 〈 /i 〉 -catenin gene by single-strand conformation polymorphism analysis and direct DNA sequencing. In addition, 40 ductal pancreatic adenocarcinomas were analyzed for intracellular β-catenin accumulation by immunohistochemistry, indicating alterations of the 〈 i 〉 β 〈 /i 〉 -catenin gene. 〈 i 〉 Results: 〈 /i 〉 Neither the 111 exocrine and endocrine pancreatic tumors nor the 14 pancreatic cancer cell lines carried mutations in exon 3 of the 〈 i 〉 β 〈 /i 〉 -catenin gene. Intracellular β-catenin accumulation was not identified in any of the 40 pancreatic adenocarcinomas. 〈 i 〉 Conclusion: 〈 /i 〉 These data suggest that the 〈 i 〉 β 〈 /i 〉 -catenin gene as the major player of the β-catenin-Tcf pathway does not play an important role in the genesis of pancreatic tumors.
    Type of Medium: Online Resource
    ISSN: 0012-2823 , 1421-9867
    RVK:
    RVK:
    Language: English
    Publisher: S. Karger AG
    Publication Date: 1999
    detail.hit.zdb_id: 1482218-0
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