A5044371850- Glioma Diagnosis and Treatment
- Nanoplatforms for cancer theranostics
- Pluripotent Stem Cells Research
- Cancer Genomics and Diagnostics
- 3D Printing in Biomedical Research
- CRISPR and Genetic Engineering
- Cancer Research and Treatments
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Nanoparticle-Based Drug Delivery
- Brain Metastases and Treatment
- Folate and B Vitamins Research
- Nuclear Physics and Applications
- Computational Drug Discovery Methods
- Histone Deacetylase Inhibitors Research
- Advanced biosensing and bioanalysis techniques
- Cerebrospinal fluid and hydrocephalus
- Cancer Cells and Metastasis
- Cell Image Analysis Techniques
- Cancer, Stress, Anesthesia, and Immune Response
- Scientific Computing and Data Management
- Dendrimers and Hyperbranched Polymers
- Protein Degradation and Inhibitors
- Single-cell and spatial transcriptomics
- PI3K/AKT/mTOR signaling in cancer
Düsseldorf University Hospital
2019-2024
Heinrich Heine University Düsseldorf
2019-2024
Essen University Hospital
2020
University of Duisburg-Essen
2011-2018
Boston University
2008
SummaryPatients with non-small cell lung cancer (NSCLC) are routinely treated cytotoxic agents such as cisplatin. Through a genome-wide siRNA-based screen, we identified vitamin B6 metabolism central regulator of cisplatin responses in vitro and vivo. By aggravating bioenergetic catastrophe that involves the depletion intracellular glutathione, exacerbates cisplatin-mediated DNA damage, thus sensitizing large panel lines to apoptosis. Moreover, sensitizes cells apoptosis induction by...
Abstract Cancer cells upregulate anabolic processes to maintain high rates of cellular turnover. Limiting the supply macromolecular precursors by targeting enzymes involved in biosynthesis is a promising strategy cancer therapy. Several tumors excessively metabolize glutamine generate for nonessential amino acids, nucleotides, and lipids, process called glutaminolysis. Here we show that pharmacological inhibition glutaminase (GLS) eradicates glioblastoma stem-like (GSCs), small cell...
The failure of a long-lasting curative therapeutic benefit currently applied chemotherapies against malignant cancers is suggested to be caused by the ineffectiveness such interventions on cancer stem cells (CSCs). CD133/AC133 cell surface protein previously shown have potential identify CSCs in various tumors, including brain tumors. Moreover, an increase rate cellular metabolism glutamine and glucose are contributors fast proliferation some high-grade malignancies. Inhibition...
Glioblastoma (GBM) is a lethal disease with limited clinical treatment options available. Recently, new inhibitor targeting the prominent cancer signaling pathway mTOR was discovered (Rapalink-1), but its therapeutic potential on stem cell populations of GBM unknown. We applied collection physiological relevant organoid-like models and studied effect RL1 exposure various cellular features as well expression targets molecules. also undertook combination treatments this agent tumor treating...
The metabolic enzyme carbonic anhydrase 12 (CA12/CAXII) emerges as a promising cancer therapeutic target with drug development projects underway. Previous reports proposed the relevance of CA12 in context glioma but are limited patient data quantity, ignore ethnic diversity patients or rely on semi-quantitative, thereby out date, methodology. Moreover, little is known association to brain tumor stemness effect anti-CAXII-directed monotherapies stem cells (GSCs), particular their response...
Abstract Nerve growth factor (NGF) is a trophic and survival for cholinergic neurons, it induces the expression of several genes that are essential synthesis storage acetylcholine (ACh), specifically choline acetyltransferase, vesicular ACh transporter (VAChT), transporter. We have found previously phosphatidylinositol 3′‐kinase pathway, but not MEK/MAPK mediator NGF‐induced differentiation. Here we demonstrate, in rat pheochromocytoma cell line PC12 primary mouse neuronal cultures,...
Stummer et al. established fluorescence-guided surgery (FGS) for glioblastoma (GBM) using 5-aminolevulinic acid (5-ALA). Its metabolite, protoporphyrin IX (PPIX), is also a photosensitizer and can be used photodynamic therapy (PDT) laser beam of 635 nm. The porphyrin derivate verteporfin (VP) was discovered to have properties penetrate the brain, pharmacologically target glioma cells, approved PDT choroidal neovascularization in wet age-related macular degeneration at 689 nm.To elucidate...
The Notch signaling network determines stemness in various tissues and targeting activity malignant brain cancers by gamma-secretase inhibitors (GSI) has shown promising preclinical success. However, the clinical translation remains challenging due to severe toxicity side effects emergence of therapy resistance. Better anti-Notch directed therapies, specifically against tumor promoting receptor 1 framework, biomarkers predicting response such are highest need. We assessed multiple patient...
<ns3:p><ns3:bold>Background:</ns3:bold> Increasing concerns emerge regarding the limited success in reproducing data and translating research results into applications. This is a major problem for science, society economy. Driven by industry or scientific networks, several attempts to combat this crisis are initiated. However, only few measures address applicability feasibility of implementation actions an academic environment with resources.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> Here...
Gold nanoparticles (Au NPs) are studied as delivery systems to enhance the effect of glutaminase1 inhibitor CB839, a promising drug candidate already in clinical trials for tumor treatments. Au NPs were synthesized using bottom-up approach and covered with polymers able bind CB839 Au-polymer-CB839 conjugate. The loading efficiency (DLE) was determined high-performance liquid chromatography characterization CB839-loaded done various microscopic spectroscopic methods. Despite chemical...
Pt-(GpG) intrastrand crosslinks are the major DNA adducts induced by platinum-based anticancer drugs. In cell lines and mouse models, persistence of these lesions correlates significantly with damage. Here we studied in circulating tumour cells (CTC) treated cisplatin medium upfront to systemic therapy from patients advanced non-small-cell lung cancer (NSCLC).Blood was drawn before treatment CD45/CD15-depleted fraction mononuclear exposed cisplatin, verified for presence CTC pan-cytokeratin...
Isocitrate dehydrogenase (IDH)-wildtype glioblastoma is the most common primary malignant brain tumor. It associated with a particularly poor prognosis, as reflected by an overall median survival of only 15 months in patients who undergo supramarginal surgical reduction tumor mass followed combined chemoradiotherapy. The highly nature IDH-wildtype thought to be driven stem-like cells (GSCs) that harbor ability self-renewal, survival, and adaptability challenging environmental conditions....
Aim: Glioblastoma is a heterogeneous lethal disease, regulated by stem-cell hierarchy and the neurotransmitter microenvironment. The identification of chemotherapies targeting individual cancer stem cells clinical need. Methodology: A robotic workstation was programmed to perform drug concentration cell-growth analysis on an in vitro model glioblastoma (GSCs). Mode-of-action selected top substance performed with manual repetition assays acquisition further parameters. Results: We identified...
The efficacy of temozolomide in melanoma treatment is low (response rate <20%) and may depend on the activity O6-methylguanine DNA methyltransferase (MGMT) mismatch repair. We identified cell lines with different sensitivities to single versus prolonged clinical dosing regimens assessed a variety potential resistance mechanisms using this model. measured mRNA expression promoter methylation MGMT essential repair genes (MLH1, MSH2). Cell cycle distribution, apoptosis/necrosis induction,...
The utility of patient-derived tumor cell lines as experimental models for glioblastoma has been challenged by limited representation the in vivo biology and low clinical translatability.Here, we report on longitudinal epigenetic transcriptional profiling seven spheroid line cultured over an extended period.Molecular profiles were associated with drug response data obtained 231 clinically used drugs.We show that remained molecularly stable displayed reproducible responses prolonged culture...
(Cell Reports 2, 257–269; August 30, 2012) In the original version of this article, published on July 26, an error was inadvertently included in Figure 6C. particular, Kaplan-Meier curves depicting disease-free survival and overall non-small cell lung carcinoma (NSCLC) patients followed at MD Anderson Cancer Center (Houston, TX, USA) were swapped, due to a labeling problem with corresponding clinical database. We have double-checked data, amended figure is provided here. The corrected now...
<ns3:p><ns3:bold>Background:</ns3:bold> Increasing concerns emerge regarding the limited success in reproducing research results. This is a major problem for science, society and economy. Driven by industry or scientific networks, several attempts to combat this crisis are initiated. However, only few measures address applicability feasibility of implementation actions into an academic environment with resources.</ns3:p><ns3:p> <ns3:bold>Methods:</ns3:bold> Here we propose strategy catalogue...
In cancer pharmacology, a drug candidate’s therapeutic potential is typically expressed as its ability to suppress cell growth. Different methods in assessing the phenotype and calculating effect have been established. However, inconsistencies response outcomes reported, it still unclear whether what extent choice of data post-processing responsible for that. Studies that systematically examine these questions are rare. Here, we compare three established calculation on collection nine vitro...
Glioblastoma (GBM) is the most commonly occurring and aggressive primary brain tumor. Transcriptomics-based tumor subtype classification has established mesenchymal lineage of GBM (MES-GBM) as cancers with particular behavior high levels therapy resistance. Previously it was show that Trihexyphenidyl (THP), a market approved M1 muscarinic receptor-targeting oral drug can suppress proliferation survival stem cells from classical transcriptomic subtype. In series
Brain metastases represent the most common intracranial tumors in adults and are associated with a poor prognosis. We used personalized vitro drug screening approach to characterize individual therapeutic vulnerabilities brain metastases.