13221
2013
eng
316
3
article
1
2016-04-15
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Anti-apoptotic signature in thymic squamous cell carcinomas – functional relevance of anti-apoptotic BIRC3 expression in the thymic carcinoma cell line 1889c
The molecular pathogenesis of thymomas and thymic arcinomas (TCs) is poorly understood and results of adjuvant therapy are unsatisfactory in case of metastatic disease and tumor recurrence. For these clinical settings, novel therapeutic strategies are urgently needed. Recently, limited sequencing efforts revealed that a broad spectrum of genes that play key roles in various common cancers are rarely affected in thymomas and TCs, suggesting that other oncogenic principles might be important.This made us re-analyze historic expression data obtained in a spectrumof thymomas and thymic squamous cell carcinomas (TSCCs) with a custom-made cDNA microarray. By cluster analysis, different anti-apoptotic signatures were detected in type B3 thymoma and TSCC, including overexpression of BIRC3 in TSCCs. This was confirmed by qRT-PCR in the original and an independent validation set of tumors. In contrast to several other cancer cell lines, the BIRC3-positive TSCC cell line, 1889c showed spontaneous apoptosis after BIRC3 knock-down. Targeting apoptosis genes is worth testing as therapeutic principle in TSCC.
Frontiers in Oncology
10.3389/fonc.2013.00316
urn:nbn:de:bvb:20-opus-132214
Frontiers in Oncology 3:316. doi: 10.3389/fonc.2013.00316
Bei Huang
Djeda Belharazem
Li Li
Susanne Kneitz
Philipp A. Schnabel
Ralf J. Rieker
Daniel Körner
Wilfried Nix
Berthold Schalke
Hans Konrad Müller-Hermelink
German Ott
Andreas Rosenwald
Philipp Ströbel
Alexander Marx
eng
uncontrolled
gene expression
eng
uncontrolled
MTCH2
eng
uncontrolled
targeted
eng
uncontrolled
myasthenia gravis
eng
uncontrolled
apoptosis
eng
uncontrolled
thymus
eng
uncontrolled
thymoma
eng
uncontrolled
thymic carcinoma
Krankheiten
open_access
Pathologisches Institut
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/13221/133_Huang_Front_Oncol.pdf
9682
2013
eng
article
1
--
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Distinct microRNA Expression Profile in Prostate Cancer Patients with Early Clinical Failure and the Impact of let-7 as Prognostic Marker in High-Risk Prostate Cancer
Background
The identification of additional prognostic markers to improve risk stratification and to avoid overtreatment is one of the most urgent clinical needs in prostate cancer (PCa). MicroRNAs, being important regulators of gene expression, are promising biomarkers in various cancer entities, though the impact as prognostic predictors in PCa is poorly understood. The aim of this study was to identify specific miRNAs as potential prognostic markers in high-risk PCa and to validate their clinical impact.
Methodology and Principal Findings
We performed miRNA-microarray analysis in a high-risk PCa study group selected by their clinical outcome (clinical progression free survival (CPFS) vs. clinical failure (CF)). We identified seven candidate miRNAs (let-7a/b/c, miR-515-3p/5p, -181b, -146b, and -361) that showed differential expression between both groups. Further qRT-PCR analysis revealed down-regulation of members of the let-7 family in the majority of a large, well-characterized high-risk PCa cohort (n = 98). Expression of let-7a/b/and -c was correlated to clinical outcome parameters of this group. While let-7a showed no association or correlation with clinical relevant data, let-7b and let-7c were associated with CF in PCa patients and functioned partially as independent prognostic marker. Validation of the data using an independent high-risk study cohort revealed that let-7b, but not let-7c, has impact as an independent prognostic marker for BCR and CF. Furthermore, we identified HMGA1, a non-histone protein, as a new target of let-7b and found correlation of let-7b down-regulation with HMGA1 over-expression in primary PCa samples.
Conclusion
Our findings define a distinct miRNA expression profile in PCa cases with early CF and identified let-7b as prognostic biomarker in high-risk PCa. This study highlights the importance of let-7b as tumor suppressor miRNA in high-risk PCa and presents a basis to improve individual therapy for high-risk PCa patients.
PLoS ONE
10.1371/journal.pone.0065064
urn:nbn:de:bvb:20-opus-96825
In: PLoS ONE (2013) 8: 6, doi:10.1371/journal.pone.0065064
Maria Schubert
Martin Spahn
Susanne Kneitz
Claus Jürgen Scholz
Steven Joniau
Philipp Stroebel
Hubertus Riedmiller
Burkhard Kneitz
eng
uncontrolled
biomarkers
eng
uncontrolled
gene expression
eng
uncontrolled
gene targeting
eng
uncontrolled
luciferase
eng
uncontrolled
MircoRNA
eng
uncontrolled
microarrays
eng
uncontrolled
oncogenes
eng
uncontrolled
prostate cancer
Medizin und Gesundheit
open_access
Urologische Klinik und Poliklinik
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9682/Schubert_journal.pone.0065064.pdf
9631
2013
eng
article
1
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DNA Methylation Mediated Control of Gene Expression Is Critical for Development of Crown Gall Tumors
Crown gall tumors develop after integration of the T-DNA of virulent Agrobacterium tumefaciens strains into the plant genome. Expression of the T-DNA–encoded oncogenes triggers proliferation and differentiation of transformed plant cells. Crown gall development is known to be accompanied by global changes in transcription, metabolite levels, and physiological processes. High levels of abscisic acid (ABA) in crown galls regulate expression of drought stress responsive genes and mediate drought stress acclimation, which is essential for wild-type-like tumor growth. An impact of epigenetic processes such as DNA methylation on crown gall development has been suggested; however, it has not yet been investigated comprehensively. In this study, the methylation pattern of Arabidopsis thaliana crown galls was analyzed on a genome-wide scale as well as at the single gene level. Bisulfite sequencing analysis revealed that the oncogenes Ipt, IaaH, and IaaM were unmethylated in crown galls. Nevertheless, the oncogenes were susceptible to siRNA–mediated methylation, which inhibited their expression and subsequently crown gall growth. Genome arrays, hybridized with methylated DNA obtained by immunoprecipitation, revealed a globally hypermethylated crown gall genome, while promoters were rather hypomethylated. Mutants with reduced non-CG methylation developed larger tumors than the wild-type controls, indicating that hypermethylation inhibits plant tumor growth. The differential methylation pattern of crown galls and the stem tissue from which they originate correlated with transcriptional changes. Genes known to be transcriptionally inhibited by ABA and methylated in crown galls became promoter methylated upon treatment of A. thaliana with ABA. This suggests that the high ABA levels in crown galls may mediate DNA methylation and regulate expression of genes involved in drought stress protection. In summary, our studies provide evidence that epigenetic processes regulate gene expression, physiological processes, and the development of crown gall tumors.
PLoS Genetics
10.1371/journal.pgen.1003267
urn:nbn:de:bvb:20-opus-96318
IZKF Laboratory for Microarray Applications, University Hospital of Wuerzburg, Wuerzburg, Germany
In: PLoS Genetics (2013) 9: 2, doi:10.1371/journal.pgen.1003267
Rosalia Deeken
Jochen Gohlke
Claus-Juergen Scholz
Susanne Kneitz
Dana Weber
Joerg Fuchs
Rainer Hedrich
eng
uncontrolled
DNA methylation
eng
uncontrolled
DNA transcription
eng
uncontrolled
gene expression
eng
uncontrolled
oncogenes
eng
uncontrolled
plant genomics
eng
uncontrolled
sequence motif analysis
eng
uncontrolled
arabidopsis thaliana
eng
uncontrolled
agrobacterium tumefaciens
Medizin und Gesundheit
open_access
Theodor-Boveri-Institut für Biowissenschaften
Julius-von-Sachs-Institut für Biowissenschaften
Förderzeitraum 2013
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/9631/Deeken_journal.pgen.1003267.pdf
11289
2014
eng
article
1
2015-05-08
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Gene Expression Profiles of Human Dendritic Cells Interacting with Aspergillus fumigatus in a Bilayer Model of the Alveolar Epithelium/Endothelium Interface
The initial stages of the interaction between the host and Aspergillus fumigatus at the alveolar surface of the human lung are critical in the establishment of aspergillosis. Using an in vitro bilayer model of the alveolus, including both the epithelium (human lung adenocarcinoma epithelial cell line, A549) and endothelium (human pulmonary artery epithelial cells, HPAEC) on transwell membranes, it was possible to closely replicate the in vivo conditions. Two distinct sub-groups of dendritic cells (DC), monocyte-derived DC (moDC) and myeloid DC (mDC), were included in the model to examine immune responses to fungal infection at the alveolar surface. RNA in high quantity and quality was extracted from the cell layers on the transwell membrane to allow gene expression analysis using tailored custom-made microarrays, containing probes for 117 immune-relevant genes. This microarray data indicated minimal induction of immune gene expression in A549 alveolar epithelial cells in response to germ tubes of A. fumigatus. In contrast, the addition of DC to the system greatly increased the number of differentially expressed immune genes. moDC exhibited increased expression of genes including CLEC7A, CD209 and CCL18 in the absence of A. fumigatus compared to mDC. In the presence of A. fumigatus, both DC subgroups exhibited up-regulation of genes identified in previous studies as being associated with the exposure of DC to A. fumigatus and exhibiting chemotactic properties for neutrophils, including CXCL2, CXCL5, CCL20, and IL1B. This model closely approximated the human alveolus allowing for an analysis of the host pathogen interface that complements existing animal models of IA.
10.1371/journal.pone.0098279
urn:nbn:de:bvb:20-opus-112893
PLoS ONE 9(5): e98279. doi:10.1371/journal.pone.0098279
Charles Oliver Morton
Mirjam Fliesser
Marcus Dittrich
Tobias Müller
Ruth Bauer
Susanne Kneitz
William Hope
Thomas Richard Rogers
Hermann Einsele
Jürgen Löffler
eng
uncontrolled
aspergillus fumigatus
eng
uncontrolled
gene expression
eng
uncontrolled
immune receptors
eng
uncontrolled
immune response
eng
uncontrolled
denritic cells
eng
uncontrolled
B cell receptors
eng
uncontrolled
gene regulation
eng
uncontrolled
RNA extraction
Medizin und Gesundheit
open_access
Medizinische Klinik und Poliklinik II
Theodor-Boveri-Institut für Biowissenschaften
Förderzeitraum 2014
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11289/097_Löffler_PLoS.pdf