- PI3K/AKT/mTOR signaling in cancer
- RNA and protein synthesis mechanisms
- Glioma Diagnosis and Treatment
- CRISPR and Genetic Engineering
- Cancer Genomics and Diagnostics
- RNA regulation and disease
- RNA modifications and cancer
- Cancer Mechanisms and Therapy
- Cancer-related molecular mechanisms research
- Alzheimer's disease research and treatments
- Nuclear Receptors and Signaling
- Cell Image Analysis Techniques
- Polyamine Metabolism and Applications
- Advanced Electron Microscopy Techniques and Applications
- Electron and X-Ray Spectroscopy Techniques
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Nanoparticles: synthesis and applications
- RNA Research and Splicing
- Skin and Cellular Biology Research
- RNA Interference and Gene Delivery
- Parkinson's Disease Mechanisms and Treatments
- Advanced MRI Techniques and Applications
- Biochemical and Molecular Research
- Lysosomal Storage Disorders Research
Medical University of Graz
2011-2023
Czech Academy of Sciences, Institute of Biophysics
2015
Colorectal cancer (CRC) is the third most common cause of related death worldwide. Furthermore, with more than 1.2 million cases registered per year, it constitutes frequent diagnosed entity Deregulation protein synthesis has received considerable attention as a major step in development and progression. Eukaryotic translation initiation factors (eIFs) are involved regulation functionally linked to phosphatidylinositol-3-kinase (PI3K)/AKT/mammalian target rapamycin (mTOR) signaling pathway....
Glioblastoma (GBM) heterogeneity, aggressiveness and infiltrative growth drastically limit success of current standard care drugs efficacy various new therapeutic approaches. There is a need for therapies models reflecting the complex biology these tumors to analyze molecular mechanisms tumor formation resistance, as well identify targets. We established screened panel 26 patient-derived subcutaneous (s.c.) xenograft (PDX) GBM on immunodeficient mice, which 15 were also orthotopic models....
Non-small cell lung cancer (NSCLC) is the leading cause of cancer-related death worldwide. Dysregulation protein synthesis plays a major role in carcinogenesis, process regulated at multiple levels, including translation mRNA into proteins. Ribosome assembly requires correct association ribosome subunits, which ensured by eukaryotic initiation factors (eIFs). eIFs have become targets therapy studies, and promising data on eIF6 various entities been reported. Therefore, we hypothesised that...
Steatohepatitis (SH) and SH-associated hepatocellular carcinoma (HCC) are of considerable clinical significance. SH is morphologically characterized by steatosis, liver cell ballooning, cytoplasmic aggregates termed Mallory-Denk bodies (MDBs), inflammation, fibrosis at late stage. Disturbance the keratin cytoskeleton aggregation keratins (KRTs) essential for MDB formation. We analyzed livers aged Krt18-/- mice that spontaneously developed in majority cases HCC independent sex. Interestingly,...
Purpose Formalin fixation prevents tissue autolysis by crosslinking proteins and changes microstructure MRI signal characteristics. Previous studies showed high variations in MR relaxation time constants of formalin fixed brain tissue, which has been attributed to the use different concentrations. Our investigations confirmed influence concentration on times unexpectedly revealed an vendor specific composition, not investigated so far. Methods We systematically analyzed human with 4% 10%...
Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Children suffering from high-risk and/or metastatic NB often show no response to therapy, and new therapeutic approaches are urgently needed. Malignant tumor development has been shown be driven by dysregulation of eukaryotic initiation factors (eIFs) at translation initiation. Especially activity heterotrimeric eIF4F complex altered in malignant cells, since it direct connection key oncogenic signaling pathways such...
Abstract Glioblastoma is characterized by widespread genetic and transcriptional heterogeneity, yet little known about the role of epigenome in glioblastoma disease progression. Here, we present genome-scale maps DNA methylation dynamics matched primary recurring tumors, based on a national population registry comprehensively annotated clinical cohort. We demonstrate feasibility mapping large set routinely collected formalin-fixed paraffin-embedded (FFPE) samples, validate bisulfite...
Glioblastoma (GBM) is an utterly devastating cerebral neoplasm and current therapies only marginally improve patients’ overall survival (OS). The PI3K/AKT/mTOR pathway participates in gliomagenesis through regulation of cell growth proliferation. Since it upstream regulator the rate-limiting translation initiation step protein synthesis, controlled by eukaryotic factors (eIFs), we aimed for a profound basic characterization 17 eIFs to identify potential novel therapeutic targets gliomas....
Biliary tract cancer (BTC) represents a malignant tumor of the biliary including cholangiocarcinoma (CCA) and carcinoma gallbladder (GBC) with 5-year survival rate between 5 18% due to late diagnosis rapid disease progression. Chronic inflammation is one main risk factors for CCA GBC in particular. IL-6, as mediator inflammation, can act through membrane-bound receptor alpha-chain (mIL-6R, "IL-6 classic signaling") or via soluble forms (sIL-6R, trans-signaling"). However, little known about...
<b><i>Background:</i></b> β-Synuclein (β-Syn) is a member of the highly homologous synuclein protein family. The most prominent family member, α-synuclein (α-Syn), abnormally accumulates in so-called Lewy bodies, one major pathological hallmarks α-synucleinopathies. Notably, parts peptide backbone, called nonamyloid component, are also found amyloid plaques. However, β-Syn seems to have beneficial effects by reducing α-Syn aggregation, and antiaggregatory activity has...
Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death. The initiation protein translation an important rate-limiting step in eukaryotes, and crucial pathogenesis many viral infections. Eukaryotic factors (eIFs) are proteins that involved linked to phosphatidylinositol-3-kinases (PI3K)/AKT/mTOR pathway. We hypothesized eIFs represent crossroads for carcinogenesis HCC might serve as potential biomarkers. immunohistochemical expression eIF subunits 2α, 3C, 3 H, 4E, 5...
Investigations of the ultrastructural features neurons and their synapses are only possible with electron microscopy. Especially for comparative studies changes in densities distributions such features, an unbiased sampling protocol is vital reliable results. Here, we present a workflow image acquisition brain samples. The allows systematic uniform random within defined region, images can be analyzed using disector. This technique much faster than extensive examination serial sections but...
Since glioma therapy is currently still limited until today, new treatment options for this heterogeneous group of tumours are great interest. Eukaryotic initiation factors (eIFs) altered in various cancer entities, including gliomas. The purpose our study was to evaluate the potential eIFs as novel targets treatment.We evaluated eIF protein expression and regulation 22 glioblastoma patient-derived xenografts (GBM PDX) after with established cytostatics regards mutation profile analyses GBM...