A5013636749- Pancreatic and Hepatic Oncology Research
- Cancer Genomics and Diagnostics
- Colorectal Cancer Treatments and Studies
- Lung Cancer Treatments and Mutations
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Gastric Cancer Management and Outcomes
- RNA modifications and cancer
- Hepatocellular Carcinoma Treatment and Prognosis
- Histone Deacetylase Inhibitors Research
- Cancer, Hypoxia, and Metabolism
- Melanoma and MAPK Pathways
- Nitric Oxide and Endothelin Effects
- Metabolism, Diabetes, and Cancer
- Genetic factors in colorectal cancer
- Cancer Cells and Metastasis
- Cancer-related Molecular Pathways
- Radiomics and Machine Learning in Medical Imaging
- Neuroendocrine Tumor Research Advances
- Renal cell carcinoma treatment
- Cancer Immunotherapy and Biomarkers
- Pancreatitis Pathology and Treatment
- Angiogenesis and VEGF in Cancer
- Veterinary Pharmacology and Anesthesia
- Cell death mechanisms and regulation
- Gastrointestinal Tumor Research and Treatment
University Hospital of Zurich
2019-2025
University of Zurich
2021-2024
University Medical Center Freiburg
2016-2024
German Cancer Research Center
2018-2024
Heidelberg University
2018-2024
University of Freiburg
2016-2022
Deutschen Konsortium für Translationale Krebsforschung
2018-2021
St. Claraspital
2021
University of Bern
2021
Novartis (China)
2020
RAS proteins are important direct activators of p110α, p110γ, and p110δ type I phosphoinositide 3-kinases (PI3Ks), interacting via an amino-terminal RAS-binding domain (RBD). Here, we investigate the regulation ubiquitous p110β isoform PI3K, implicated in G-protein-coupled receptor (GPCR) signaling, PTEN-loss-driven cancers, thrombocyte function. Unexpectedly, is unable to interact with p110β, but instead RAC1 CDC42 from RHO subfamily small GTPases bind activate its RBD. In fibroblasts,...
RAC1 P29 is the third most commonly mutated codon in human cutaneous melanoma, after BRAF V600 and NRAS Q61. Here, we study role of RAC1P29S melanoma development reveal that activates PAK, AKT, a gene expression program initiated by SRF/MRTF transcriptional pathway, which results melanocytic to mesenchymal phenotypic switch. Mice with ubiquitous from endogenous locus develop lymphoma. When expressed only melanocytes, cooperates oncogenic or NF1-loss promote tumorigenesis. also drives...
Dramatic advances in our understanding of the molecular pathophysiology cancer, along with a rapidly expanding portfolio targeted drugs, have led to paradigm shift toward personalized, biomarker-driven cancer treatment. Here, we report 2-year experience Comprehensive Cancer Center Freiburg Molecular Tumor Board (MTB), one first interdisciplinary tumor conferences established Europe. The role MTB is recommend personalized therapy for patients beyond standard-of-care
Objectives: To analyze long-term oncological outcome along with prognostic risk factors in a large cohort of patients colorectal liver metastases (CRLM) undergoing ALPPS. Background: ALPPS is two-stage hepatectomy variant that increases resection rates and R0 primarily unresectable CRLM as evidenced recent randomized controlled trial. Long-term oncologic results, however, are lacking. Methods: Cases in- outside the International Registry were collected completed by direct contacts to centers...
Objective: Volume depletion and/or increased hematocrit are associated with poor prognosis in necrotizing pancreatitis. Several studies suggest that intrathoracic blood volume index (ITBI) might be superior to central venous pressure (CVP) regard preload assessment. Therefore, the aim of our study was evaluate predictive value CVP and ITBI, correlate these parameters cardiac (CI). Design: Prospective study. Setting: Medical intensive care unit, university hospital. Patients Interventions:...
Inhibitor of κB (IκB) β (IκBβ) represents one the major primary regulators NF-κB in mammals. In contrast to defined regulatory interplay between and IκBα, much less is known about biological function IκBβ. To elucidate physiological role IκBβ signaling vivo, we generated IκBβ-deficient mice. These animals proved be highly refractory LPS-induced lethality, accompanied by a strong reduction sepsis-associated cytokine production. response LPS, recruited IL-1β promoter forming complex with...
Pancreatic ductal adenocarcinoma (PDAC) is a devastating disease. Circulating tumor cells (CTC) in the blood are hypothesized as means of systemic spread. Blood obtained from healthy donors and patients with PDAC was therefore subject to size-based CTC-isolation. We additionally compared Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations pancreatic CTC corresponding tumors, evaluated their significance prognostic markers. Samples 68 individuals (58 patients, 10 donors) were...
PI3Kβ mediates synergistic signaling upon costimulation of GPCRs and receptor tyrosine kinases in immune cells.
Molecular precision oncology faces two major challenges: first, to identify relevant and actionable molecular variants in a rapidly changing field second, provide access broad patient population. Here, we report four-year experience of the Tumor Board (MTB) Comprehensive Cancer Center Freiburg (Germany) including workflows process optimizations. This retrospective single-center study includes data on 488 patients enrolled MTB from February 2015 through December 2018. Recommendations include...
The integrated stress response (ISR) integrates a broad range of environmental and endogenous signals to the phosphorylation α-subunit eukaryotic translation initiation factor 2 (eIF2α). Although intense or prolonged activation this pathway is known induce apoptosis, molecular mechanisms coupling stress-induced eIF2α cell death machinery have remained incompletely understood. In study, we characterized apoptosis in classical activators ISR (tunicamycin, UVC, elevated osmotic pressure,...
Purpose: To prospectively compare the protective effect of acetylcysteine, theophylline, and both agents combined in patients who are admitted to intensive care unit with at least one risk factor for contrast material–induced nephropathy receive 100 mL iodinated medium. Materials Methods: Institutional ethics review board approval informed consent were obtained. A total 91 (mean age, 58.5 years ± 14.8 [standard deviation]; 31 women, 60 men; 150 examinations) contrast-induced received either...
Late diagnosis and systemic dissemination essentially contribute to the invariably poor prognosis of pancreatic ductal adenocarcinoma (PDAC). Therefore, development diagnostic biomarkers for PDAC are urgently needed improve patient stratification outcome in clinic. By studying transcriptomes independent cohorts tumor non-tumor tissues, we identified 81 robustly regulated genes, through a novel, generally applicable meta-analysis. Using consensus clustering on co-expression values revealed...
To evaluate the role of ablative radiotherapy doses in treatment hilar or intrahepatic cholangiocarcinoma (CCC) using stereotactic body (SBRT).Consecutive patients treated from 2007 to 2016 with CCC were evaluated. Local control and toxicities assessed every 3 months according Response Evaluation Criteria In Solid Tumors (RECIST) Common Terminology for Adverse Events v4.0, respectively. Overall survival (OS), local (LC) progression free calculated SBRT.Thirty seven 43 lesions retrospectively...
Targeted next generation sequencing (tNGS) has become part of molecular pathology diagnostics for determining RAS mutation status in colorectal cancer (CRC) patients as predictive tool decision on EGFR-targeted therapy. Here, we investigated profiles case-matched tissue specimens throughout the disease course CRC, to further specify RAS-status dynamics and identify de novo mutations associated with distant metastases. Case-matched formalin-fixed paraffin-embedded (FFPE) resection (n = 70;...
Abstract Background Novel biomarkers and molecular monitoring tools hold potential to improve outcome for patients following resection of pancreatic ductal adenocarcinoma (PDAC). We hypothesized that the combined longitudinal analysis mutated cell-free plasma KRAS (cf mu t ) CA 19–9 during adjuvant treatment follow-up might more accurately predict disease course than hitherto available parameters. Methods Between 07/2015 10/2018, we collected 134 samples from 25 after R0/R1-resection PDAC...
We evaluated circulating tumor DNA (ctDNA) for detecting burden in melanoma and examined whether early changes the number of ctDNA copies predict response to treatment.We included 12 patients with stage III 50 IV BRAF exon 15 or NRAS 3 mutations tissue. used droplet digital polymerase chain reaction retrospectively analyze serial plasma samples mutation-positive ctDNA.Matched serum were positive ctDNA, lactate dehydrogenase, S100 113 (45.8%), 108 (43.7%; not significant), 58 (23.5%; P <...