A5060020593- Caveolin-1 and cellular processes
- Peroxisome Proliferator-Activated Receptors
- Metabolism, Diabetes, and Cancer
- Cancer Immunotherapy and Biomarkers
- Cancer, Hypoxia, and Metabolism
- Cancer, Lipids, and Metabolism
- Epigenetics and DNA Methylation
- Helicobacter pylori-related gastroenterology studies
- Histone Deacetylase Inhibitors Research
- Pancreatic and Hepatic Oncology Research
- Signaling Pathways in Disease
- Genetic factors in colorectal cancer
- Protein Kinase Regulation and GTPase Signaling
- Liver Disease Diagnosis and Treatment
- Peptidase Inhibition and Analysis
- Drug Transport and Resistance Mechanisms
- Cancer Cells and Metastasis
- Cancer Research and Treatments
- NF-κB Signaling Pathways
- PI3K/AKT/mTOR signaling in cancer
- Immune Cell Function and Interaction
- Cytokine Signaling Pathways and Interactions
- Esophageal Cancer Research and Treatment
- Colorectal Cancer Treatments and Studies
- Adipose Tissue and Metabolism
University Medical Centre Mannheim
2016-2025
Heidelberg University
2016-2025
University Hospital Heidelberg
2016-2025
Medizinische Fakultät Mannheim
2013-2024
Heidelberg University
2019
Central Institute of Mental Health
2014
American Gastroenterological Association
2012
American College of Gastroenterology
2012
American Association for the Study of Liver Diseases
2012
Klinikum rechts der Isar
2007-2010
Abstract In colorectal cancer (CRC), aberrant Wnt signalling is essential for tumorigenesis and maintenance of stem cells. However, how other oncogenic pathways converge on to modulate cell homeostasis in CRC currently remains poorly understood. Using large-scale compound screens CRC, we identify MEK1/2 inhibitors as potent activators Wnt/β-catenin signalling. Targeting MEK increases activity different lines murine intestine vivo. Truncating mutations APC generated by CRISPR/Cas9 strongly...
Chemotherapy for advanced colorectal cancer leads to improved survival; however, predictors of response systemic treatment are not available. Genomic and epigenetic alterations the gene encoding transcription factor AP-2 epsilon (TFAP2E) common in human cancers. The dickkopf homolog 4 protein (DKK4) is a potential downstream target TFAP2E has been implicated chemotherapy resistance. We aimed further evaluate role DKK4 as chemotherapy.
The mitogen-activated protein kinase (MAPK)/extracellular signal-regulated (ERK) cascade plays a central role in intracellular signaling by many extracellular stimuli. One target of the ERK is peroxisome proliferator-activated receptor gamma (PPARgamma), nuclear that promotes differentiation and apoptosis. It was previously demonstrated PPARgamma activity attenuated upon mitogenic stimulation due to phosphorylation its Ser84 ERKs. Here we show tetradecanoyl phorbol acetate (TPA) attenuates...
Abstract Patient-derived organoids resemble the biology of tissues and tumors, enabling ex vivo modeling human diseases. They have heterogeneous morphologies with unclear biological causes relationship to treatment response. Here, we use high-throughput, image-based profiling quantify phenotypes over 5 million individual colorectal cancer after >500 small molecules. Integration data using multi-omics identifies axes morphological variation across organoids: Organoid size is linked IGF1...
Partial agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma), also termed selective PPARgamma modulators, are expected to uncouple insulin sensitization from triglyceride (TG) storage in patients with type 2 diabetes mellitus. These agents shall thus avoid adverse effects, such as body weight gain, exerted by full thiazolidinediones. In this context, we describe the identification and characterization isoquinoline derivative PA-082, a prototype novel class...
Measurements of target activation in cells or tissues are key indicators efficacy during drug development. In contrast to established methods that require reagents and multiple preprocessing steps, reagent-free situ analysis engaged targets target-proximal pharmacodynamic signatures solid tumors remains challenging. Here, we demonstrate label-free quantification histone acetylation-specific mass shifts by matrix-assisted laser desorption ionization (MALDI) spectrometry biotyping can be used...
The identification of new biomarkers and the development novel, targetable contexts vulnerability are urgent clinical need in drug-resistant metastatic colorectal cancer (mCRC). Aryl-Hydrocarbon-Receptor-Nuclear-Translocator-Like (ARNTL/BMAL1) is a circadian clock-regulated transcription factor promoting expression genes involved angiogenesis tumour progression. We hypothesised that BMAL1 increases vascular endothelial growth A VEGFA gene and, thereby, confers resistance to anti-angiogenic...
The overall survival of patients with advanced and refractory oesophageal squamous cell carcinoma, mostly aged 65 years older, is poor. Treatment PD-1 antibodies showed improved progression-free survival. We assessed the safety efficacy combined nivolumab ipilimumab therapy in this population.This multicentre, open-label, phase 2 trial done 32 sites Germany included older carcinoma disease progression or recurrence following first-line therapy. Patients were treated (240 mg fixed dose once...
Abstract Caveolin-1 is a scaffold protein of caveolae that acts as tumor modulator by interacting with cell adhesion molecules and signaling receptors. The role caveolin-1 in the pathogenesis gastric cancer (GC) currently unknown. We show confocal immunofluorescence microscopy immunohistochemistry biopsies from GC patients (n = 41) nonneoplastic mucosa expressed foveolar epithelial cells adjacent connective tissue. only 3 41 (7%) were all intestinal type. Quantitative PCR Western blotting...
Gastric cancer (GC) remains a malignant disease with high mortality. Patients are frequently diagnosed in advanced stages where survival prognosis is poor. Thus, there medical need to find novel drug targets and treatment strategies. Recently, the comprehensive molecular characterization of GC subtypes revealed mutations small GTPase RHOA as hallmark diffuse-type GC. activates RHO-associated protein kinases (ROCK1/2) which regulate cell contractility, migration growth thus may play role...
Peroxisome proliferator‐activated receptor‐gamma (PPAR γ ) exerts multiple functions in determination of cell fate, tissue metabolism, and host immunity. Two synthetic PPAR ligands (rosiglitazone pioglitazone) were approved for the therapy type‐2 diabetes mellitus are expected to serve as novel cures inflammatory diseases cancer. However, its exhibit a janus‐face behaviour tumor modulators various systems, resulting either suppression or promotion. This may be part due signaling crosstalk...
Bile acids from duodenogastric reflux promote inflammation and increase the risk for gastro-oesophageal cancers. FXR (farnesoid X receptor/NR1H4) is a transcription factor regulated by bile such as CDCA (chenodeoxycholic acid). protects liver intestinal tract against acid overload; however, functional role in stomach has not been described. We detected expression normal human GC (gastric cancer). mRNA protein were also present cell lines MKN45 SNU5, but AGS line. Transfection of into cells...
Peroxisome proliferator-activated receptor γ (PPARγ) is a transcription factor that promotes differentiation and cell survival in the stomach. PPARγ upregulates interacts with caveolin-1 (Cav1), scaffold protein of Ras/mitogen-activated kinases (MAPKs). The cytoplasmic-to-nuclear localization altered gastric cancer (GC) patients, suggesting so-far-unknown role for Cav1 spatial regulation signaling. We show here loss accelerated proliferation normal stomach GC cells vitro vivo. Downregulation...
Advanced esophageal squamous cell cancer (ESCC) is frequently diagnosed in elderly patients. The impact of 2nd line chemotherapy poorly defined. Recent data demonstrated effectiveness checkpoint inhibitors different carcinomas. Therefore, we assess combined nivolumab/ipilimumab as therapy ESCC RAMONA a multicenter open-label phase II trial. primary objective to demonstrate significant survival benefit advanced compared historical standard chemotherapy. Primary endpoint therefore overall...
With the development of direct acting antiviral agents (DAA) chronic hepatitis C virus (HCV) infection has become curable in most patients. Since HCV is known to have and/or indirect effects on glucose metabolism, successful treatment may an impact reducing level, pre-diabetes, need for diabetes, and ultimately diabetes-associated morbidity. We investigated association DAA metabolism context or resolution hepatic fibrosis a large cohort HCV- infected patients.In this retrospective...