A5087019197- Pancreatic and Hepatic Oncology Research
- Heat shock proteins research
- Cancer, Hypoxia, and Metabolism
- Ubiquitin and proteasome pathways
- Cancer Genomics and Diagnostics
- RNA modifications and cancer
- Endoplasmic Reticulum Stress and Disease
- Peptidase Inhibition and Analysis
- Cancer Cells and Metastasis
- Epigenetics and DNA Methylation
- Renal and related cancers
- PARP inhibition in cancer therapy
- ATP Synthase and ATPases Research
- Pancreatic function and diabetes
- Prostate Cancer Treatment and Research
- Pluripotent Stem Cells Research
- Adenosine and Purinergic Signaling
- Telomeres, Telomerase, and Senescence
- PI3K/AKT/mTOR signaling in cancer
- NF-κB Signaling Pathways
- Radiation Therapy and Dosimetry
- Chronic Lymphocytic Leukemia Research
- Genetic factors in colorectal cancer
- Cancer Research and Treatments
- Cancer Mechanisms and Therapy
University Hospital Ulm
2014-2025
Universität Ulm
2014-2024
Justus-Liebig-Universität Gießen
2011
Martin Luther University Halle-Wittenberg
2011
KU Leuven
2011
Friedrich-Alexander-Universität Erlangen-Nürnberg
2011
Boston Children's Hospital
2007
The transcription factor NF-κB is activated in a range of human cancers and thought to promote tumorigenesis, mainly due its ability protect transformed cells from apoptosis. To investigate the role epithelial plasticity metastasis, we utilized well-characterized vitro/in vivo model mammary carcinogenesis that depends on collaboration Ha-Ras oncoprotein TGF-β. We show here IKK-2/IκBα/NF-κB pathway required for induction maintenance epithelial-mesenchymal transition (EMT). Inhibition...
The transcription factor NF-κB is activated in a range of human cancers and thought to promote tumorigenesis, mainly due its ability protect transformed cells from apoptosis. To investigate the role epithelial plasticity metastasis, we utilized well-characterized vitro/in vivo model mammary carcinogenesis that depends on collaboration Ha-Ras oncoprotein TGF-β. We show here IKK-2/IκBα/NF-κB pathway required for induction maintenance epithelial-mesenchymal transition (EMT). Inhibition...
Initially identified as a molecule that regulates the final step of glycolysis, M2 isoform pyruvate kinase (PKM2) was recently reported to have central role in metabolic reprogramming cancer cells well participating cell cycle progression and gene transcription. Despite intensive efforts, intricate molecular mechanisms through which PKM2 tumor remain elusive.The proliferation apoptosis various pancreatic using lentiviral-mediated abrogation were assessed vitro via Western blot flow...
Next‐generation sequencing has become a cornerstone of therapy guidance in cancer precision medicine and an indispensable research tool translational oncology. Its rapidly increasing use during the last decade expanded options for targeted tumor therapies, molecular boards have grown accordingly. However, with detection genetic alterations, their interpretation more complex error‐prone, potentially introducing biases reducing benefits clinical practice. To facilitate interdisciplinary...
Pancreatic ductal adenocarcinomas (PDAC) harbor recurrent functional mutations of the master DNA damage response kinase ATM, which has been shown to accelerate tumorigenesis and epithelial-mesenchymal transition. To study how ATM deficiency affects genome integrity in this setting, we evaluated molecular effects conditional Atm deletion a mouse model PDAC. was associated with increased mitotic defects, genomic rearrangements, deregulated checkpoints, reminiscent human We hypothesized that...
(ATM) is the most frequently mutated DNA damage response gene, involved in homologous recombination (HR), pancreatic ductal adenocarcinoma (PDAC).
Pancreatic ductal adenocarcinoma (PDAC) often arises from preexisting cystic lesions such as intraductal papillary mucinous neoplasms (IPMN) and (MCN). This study investigated the molecular heterogeneity mutational landscape of MCN in relation to PDAC, highlighting significance KRAS mutations tumor progression. Utilizing targeted next-generation sequencing on low-grade invasive PDAC samples, we identified a substantial overlap profiles, particularly KRAS, TP53, FBXW7. Specifically, 69.2%...
<h3>Background</h3> Tumour angiogenesis is crucially dependent on the communication between tumour and associated endothelium. Protein kinase D (PKD) isoenzymes mediate vascular endothelial growth factor-A (VEGF-A) induced cell proliferation migration are also highly expressed in various tumours. <h3>Aim</h3> To examine role of PKDs for selectively pancreatic gastric tumours tumour-associated endothelium vitro vivo. <h3>Methods</h3> PKD2 expression human was determined by...
Previous efforts to develop drugs that directly inhibit the activity of mutant KRAS, most commonly mutated human oncogene, have not been successful. Cancer cells driven by KRAS require expression serine/threonine kinase STK33 for their viability and proliferation, identifying as a context-dependent therapeutic target. However, specific strategies interfering with critical functions are yet available. Here, using mass spectrometry-based screen protein interaction partners, we report...
Abstract The kinase PRKD2 (protein D) is a crucial regulator of tumor cell-endothelial cell communication in gastrointestinal tumors and glioblastomas, but its mechanistic contributions to malignant development are not understood. Here, we report that the oncogenic chaperone HSP90 binds stabilizes human cancer cells. Pharmacologic inhibition with structurally divergent small molecules currently clinical triggered proteasome-dependent degradation PRKD2, augmenting apoptosis cells various...
HSP90 is a ubiquitously expressed molecular chaperone implicated in the correct folding and maturation of plethora proteins including protein kinases transcription factors. While disruption activity was associated with augmented cancer cell death decreased tumor growth both vitro vivo, regulation not clearly understood. Here we report that treatment cells cold physical plasma, an emerging less aggressive therapy, resulted ROS generation which subsequently triggered cleavage HSP90. Notably,...
Dysregulated intestinal epithelial apoptosis initiates gut injury, alters the barrier, and can facilitate bacterial translocation leading to a systemic inflammatory response syndrome (SIRS) and/or multi-organ dysfunction (MODS). A variety of gastrointestinal disorders, including bowel disease, have been linked apoptosis. Similarly, hyperpermeability failure occur in critically ill patients, putting at center SIRS pathology. Regulation immune-modulatory functions ascribed...
Phospholipid-hydroperoxide glutathione peroxidase (PHGPx) exhibits high specific activity in reducing phosphatidylcholine hydroperoxides (PCOOHs) and thus may play a central role protecting the skin against UV irradiation-triggered detrimental long term effects like cancer formation premature aging. Here we addressed of PHGPx protection irradiation-induced expression matrix metalloproteinase-1 (MMP-1). For this purpose, created human dermal fibroblast cell lines overexpressing PHGPx....
Glioblastoma multiforme, a highly aggressive tumor of the central nervous system, has dismal prognosis that is due in part to its resistance radio- and chemotherapy. The protein kinase C (PKC) family serine threonine kinases been implicated formation proliferation glioblastoma multiforme. Members D (PKD) family, which consists PKD1, -2 and, -3, are prominent downstream targets PKCs could play major role growth. PKD2 was expressed both low-grade high-grade human gliomas. number PKD2-positive...
Myxoid liposarcomas (MLS), malignant tumors of adipocyte origin, are driven by the FUS-DDIT3 fusion gene encoding an aberrant transcription factor. The mechanisms whereby mediates sarcomagenesis incompletely understood, and strategies to selectively target MLS cells remain elusive. Here we show, using unbiased functional genomic approach, that FUS-DDIT3-expressing mesenchymal stem cell lines dependent on YAP1, a transcriptional co-activator central effector Hippo pathway involved in tissue...
Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive and metastatic malignancies worldwide. Migrating cancer stem cells (miCSCs) marked by CD133+CXCR4+ expression drives metastasis but lacks effective drug targets. Here, we show that activated pancreatic stellate secrete CXCR4 ligand CXCL12 to foster stemness, epithelial-to-mesenchymal transition (EMT), chemoresistance. Protein interaction network analyses links CXCL12/CXCR4 signaling axis downstream transcription factor...
Adenosine is a signaling molecule that exerts dual effects on tumor growth: while it inhibits immune cell function and thereby prevents surveillance by the system, influences tumorigenesis directly via activation of adenosine receptors cells at same time. However, adenosine-mediated mechanisms affecting oncogenic processes particularly in head neck squamous carcinomas (HNSCC) are not fully understood. Here, we investigated role receptor activity HNSCC-derived lines. Targeting A2B (ADORA2B)...
To assess the role of telomerase activity and telomere length in pancreatic CSCs we used different CSC enrichment methods (CD133, ALDH, sphere formation) primary patient-derived cancer cells. We show that have higher longer telomeres than bulk tumor Inhibition activity, using genetic knockdown or pharmacological inhibitor (BIBR1532), resulted marker depletion, abrogation formation vitro reduced tumorigenicity vivo. Furthermore, identify a positive feedback loop between stemness factors...
Patient-derived induced pluripotent stem cells (iPSCs) provide a unique platform to study hereditary disorders and predisposition syndromes by resembling germline mutations of affected individuals their potential differentiate into nearly every cell type the human body. We employed plucked hair from two siblings with family history cancer carrying pathogenic CDKN2A variant, P16-p.G101W/P14-p.R115L, generate patient-specific iPSCs in cancer-prone ancestry for downstream analytics. The...
Lately, the HSP90 client serine/threonine kinase STK33 emerged to be required by cancer cells for their viability and proliferation. However, its mechanistic contribution carcinogenesis is not clearly understood. Here we report that elevated expression correlates with advanced stages of human pancreatic colorectal carcinomas. Impaired proliferation augmented apoptosis associated genetic abrogation were paralleled decreased vascularization in tumor xenografts. In line this, ectopic only...