A5063196498- T-cell and Retrovirus Studies
- Cutaneous lymphoproliferative disorders research
- NF-κB Signaling Pathways
- CRISPR and Genetic Engineering
- Melanoma and MAPK Pathways
- Cancer Treatment and Pharmacology
- Biosimilars and Bioanalytical Methods
- Economic and Financial Impacts of Cancer
- Neuroblastoma Research and Treatments
- Colorectal Cancer Treatments and Studies
- HER2/EGFR in Cancer Research
- interferon and immune responses
- RNA regulation and disease
- Cancer therapeutics and mechanisms
- PI3K/AKT/mTOR signaling in cancer
- Toxin Mechanisms and Immunotoxins
- Cytokine Signaling Pathways and Interactions
- Multiple Myeloma Research and Treatments
- Immune Cell Function and Interaction
- Ubiquitin and proteasome pathways
- Cancer survivorship and care
- Machine Learning in Healthcare
- Lung Cancer Treatments and Mutations
- Cell death mechanisms and regulation
- Hippo pathway signaling and YAP/TAZ
University Hospital of Zurich
2014-2024
University of Zurich
2015-2024
Breast Center
2024
Brustzentrum Klinik St. Anna
2023-2024
German Cancer Research Center
2007-2023
Heidelberg University
2007-2023
See-Spital
2023
University Hospital Heidelberg
2013
Dana-Farber Cancer Institute
2004
Harvard University
2004
Systematic exploration of cancer cell vulnerabilities can inform the development novel therapeutics. Here, through analysis genome-scale loss-of-function datasets, we identify adenosine deaminase acting on RNA (ADAR or ADAR1) as an essential gene for survival a subset lines. ADAR1-dependent lines display increased expression interferon-stimulated genes. Activation type I interferon signaling in context ADAR1 deficiency induce lethality non-ADAR1-dependent ADAR deletion causes activation...
Reactive oxygen species (ROS) play a key role in regulation of activation-induced T-cell death (AICD) by induction CD95L expression. However, the molecular source and signaling steps necessary for ROS production are largely unknown. Here, we show that proximal receptor-signaling machinery, including ZAP70 (zeta chain-associated protein kinase 70), LAT (linker activated T cells), SLP76 (SH2 domain-containing leukocyte 76 kDa), PLCgamma1 (phospholipase Cgamma1), PKCtheta (protein Ctheta),...
Abstract Aberrant signaling of the nuclear facotr (NF-κB) pathway has been identified as a mediator survival and apoptosis resistance in leukemias lymphomas. Here, we report that cell death cutaneous T-cell lymphoma lines induced by inhibition NF-κB is independent caspases or classic receptors. We found free intracellular iron reactive oxygen species (ROS) are main mediators this death. Antioxidants such N-Acetyl-l-cysteine glutathione chelator desferrioxamine effectively block primary T...
Metformin pharmacokinetics depends on the presence and activity of membrane-bound drug transporters may be affected by transport inhibitors. The aim this study was to investigate effects trimethoprim metformin genetic modulation organic cation transporter 2 (OCT2) multidrug toxin extrusion 1 (MATE1) polymorphisms.Twenty-four healthy volunteers received 500 mg three times daily for 10 days 200 twice from day 5 10. Effects steady-state were analysed.In population as a whole, significantly...
// Michael K. Kiessling 1, 2 , Alessandra Curioni-Fontecedro Panagiotis Samaras Kirstin Atrott 1 Jesus Cosin-Roger 3 Silvia Lang Scharl Gerhard Rogler Division of Gastroenterology and Hepatology, University Hospital Zurich, Switzerland Oncology, Department Pharmacology CIBERehd, Faculty Medicine, Valencia, Spain Correspondence to: Kiessling, e-mail: Michael.kiessling@usz.ch Keywords: HRAS mutations, MEK inhibitor, mTOR lung cancer, bladder cancer Received: March 23, 2015 Accepted: October...
Genome-wide CRISPR-Cas9 dropout screens can identify genes whose knockout affects cell viability. Recent CRISPR detected thousands of essential required for cellular survival and key processes; however discovering novel lineage-specific genetic dependencies from the many hits still remains a challenge. To assess whether help cancer dependencies, we screened two human lines carrying known distinct oncogenic mutations using genome-wide sgRNA library. We found that gRNA targeting driver...
High-risk neuroblastoma remains lethal in about 50% of patients despite multimodal treatment. Recent attempts to identify molecular targets for specific therapies have shown that Neuroblastoma RAS (NRAS) is significantly mutated a small number patients. However, few inhibitors the potential treatment NRAS mutant been investigated so far. In this in-vitro study, we show MEK AZD6244, MEK162 and PD0325901 block cell growth lines but not wild-type lines. Several studies leads PI3K pathway...
Anaplastic lymphoma kinase (ALK) rearrangements are known oncogenic drivers in non-small cell lung cancer (NSCLC). Few case reports described the occurrence of such large neuroendocrine carcinomas (LCNECs) without information on clinical responses to ALK tyrosine inhibitors (TKIs) these cases. Currently, tumors lungs not screened for rearrangements.To illustrate impact molecular characterization LCNECs, we report disease course three patients with ALK-rearranged metastatic LCNEC from our...
Trastuzumab has had a major impact on the treatment of human epidermal growth factor receptor 2 (HER2)-positive breast cancer (BC). Anti-HER2 biosimilars such as Ogivri have demonstrated safety and clinical equivalence to trastuzumab (using Herceptin reference product) in trials. To our knowledge, there been no real-world report side effects quality life (QoL) patients treated with using electronic patient-reported outcomes (ePROs).
Background The evaluation of electronic patient-reported outcomes (ePROs) is increasingly being used in clinical studies patients with cancer and enables structured standardized data collection patients’ everyday lives. So far, few or analyses have focused on the medical benefit ePROs for patients. Objective current exploratory analysis aimed to obtain an initial indication whether use Consilium Care app (recently renamed medidux; mobile Health AG) regular self-assessment side effects by had...
NF‐κB is a crucial transcription factor regulating apoptosis sensitivity and resistance. It has been shown that inhibition of in T lymphocytes leads to sensitization towards apoptosis. The underlying molecular mechanism not entirely understood. Therefore, we investigated cell receptor (TCR) stimulated cells which activity blocked by an inhibitor or IκBα overexpression. We show enhanced upon TCR stimulation caspase‐ JNK‐dependent, but independent the CD95/CD95L system. Generation reactive...
Therapy of cutaneous T cell lymphoma (CTCL) is complicated by a distinct resistance the malignant cells towards apoptosis that can be caused NRAS mutations in late-stage patients. These correlate with decreased overall survival, but sensitize respective CTCL MEK-inhibition-induced which represents promising novel therapeutic target CTCL. Here, we show multi-kinase inhibitor Sorafenib induces NRAS-mutated cells. lines and to minor extent primary from Sézary patients without are also affected...
Biosimilars are increasingly being licensed as equipotent drugs, although efficacy and safety data not available for all clinical indications. Accordingly, the of biosimilar filgrastim Zarzio® combined with vinorelbine chemo‐mobilization CD34+ hematopoietic progenitor cells (HPC) in patients multiple myeloma has been evaluated yet. We compared this HPC mobilization to plus original (Neupogen®). Overall, 105 received 35 mg/m 2 intravenously on day 1 either ( n = 61;58%) or 44;42%) at a dose 5...
11082 Background: HRAS (Harvey-RAS) is a frequently mutated oncogene in cancer. head and neck cancer (3.9%), bladder (5.1%), vulvar squamous cell carcinoma (9.3%), cutaneous lung (3.8%). However, mutant as drug target has not been investigated so far. Methods: Cell Proliferation Viability Assays: proliferation was measured with the Cell-Titer-Glo Reagent (Promega) according to manufacturer's instructions. Cells were plated clear-bottomed 96-well plates at density of 500 - 2500 cells per...
Background The use of smartphone apps in cancer patients undergoing systemic treatment can promote the early detection symptoms and therapy side effects may be supported by machine learning (ML) for timely adaptation therapies reduction adverse events unplanned admissions. Objective We aimed to create an Early Warning System (EWS) predict situations where supportive interventions become necessary prevent visits. For this, dynamically collected standardized electronic patient reported outcome...