- Cancer Genomics and Diagnostics
- Cancer Cells and Metastasis
- Extracellular vesicles in disease
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Single-cell and spatial transcriptomics
- Cancer-related molecular mechanisms research
- Genetic factors in colorectal cancer
- Cancer Immunotherapy and Biomarkers
- Innovative Microfluidic and Catalytic Techniques Innovation
- RNA and protein synthesis mechanisms
- Urinary and Genital Oncology Studies
- RNA Research and Splicing
- Cancer Diagnosis and Treatment
- Advanced Proteomics Techniques and Applications
- Bladder and Urothelial Cancer Treatments
- Glycosylation and Glycoproteins Research
- Immunotherapy and Immune Responses
- Cancer-related gene regulation
- Pancreatic and Hepatic Oncology Research
- Molecular Biology Techniques and Applications
- CRISPR and Genetic Engineering
- Breast Cancer Treatment Studies
- Cancer Research and Treatments
- Circular RNAs in diseases
Clinical Hospital No. 8
2024
Universität Hamburg
2010-2020
University Medical Center Hamburg-Eppendorf
2010-2020
Qiagen (Germany)
2019
Research Centre for Medical Genetics
2010
Circulating tumor cells (CTCs) hold great potential to answer key questions of how non-small cell lung cancer (NSCLC) evolves and develops resistance upon anti-PD-1/PD-L1 treatment. Currently, their clinical utility in NSCLC is compromised by a low detection rate with the established, Food Drug Administration (FDA)-approved, EpCAM-based CellSearch® System. We tested an epitope-independent method (ParsortixTM system) utilized it assess PD-L1 expression CTCs from patients. prospectively...
Endocrine treatment is the most preferable systemic in metastatic breast cancer patients that have had an estrogen receptor (ER) positive primary tumor or lesions, however, approximately 20% of these do not benefit from therapy and demonstrate further progress. One reason for failure endocrine might be heterogeneity ER expression cells spreading to distant sites which reflected detectable circulating (CTCs).A sensitive specific staining protocol ER, keratin 8/18/19, CD45 was established....
In cancer patients, circulating cell-free DNA (ccfDNA) can contain tumor-derived (ctDNA), which enables noninvasive diagnosis, real-time monitoring, and treatment susceptibility testing. However, ctDNA fractions are highly variable, challenges downstream applications. Therefore, established preanalytical work flows in combination with cost-efficient reproducible reference materials for ccfDNA analyses crucial analytical validity subsequently clinical decision-making.We describe the efforts...
ABSTRACT Cells release heterogeneous nano‐sized vesicles either as exosomes, being derived from endosomal compartments, or through budding the plasma membrane so‐called microvesicles, commonly referred to extracellular (EVs). EVs are known for their important roles in mammalian physiology and disease pathogenesis provide a potential biomarker source cancer patients. generally often analysed bulk using Western blotting by bead‐based flow‐cytometry or, with limited parameters, nanoparticle...
Progress in sensitive analytical approaches has opened new avenues for the detection of cells or products such as circulating cell-free DNA released by tumors. These 'liquid biopsies' are being explored clinical trials early cancer detection, prediction recurrent disease, and assessment therapeutic resistance mechanisms.
Circulating tumor cells (CTCs) are important clinical indicators for prognosis and treatment efficacy. However, CTC investigation is hampered by their low number, making the establishment of permanent lines very challenging. We derived characterized nine using blood samples from a patient with metastatic colorectal cancer collected before after chemotherapy targeted therapy, during progression. These cell displayed an intermediate epithelial/mesenchymal phenotype, stem-cell like...
Whole genome amplification (WGA) is required for single cell genotyping. Effectiveness of currently available WGA technologies in combination with next generation sequencing (NGS) and material preservation still elusive.In respect to the accuracy SNP/mutation, indel, copy number aberrations (CNA) calling, HiSeq2000 platform outperformed IonProton all aspects. Furthermore, more accurate SNP/mutation indel calling was demonstrated using tumor cells obtained from EDTA-collected blood...
Despite remarkable progress in melanoma therapy, the exceptional heterogeneity of disease has prevented development reliable companion biomarkers for prediction or monitoring therapy responses. Here, we show that difficulties detecting blood-based markers, like circulating tumor cells (CTC), might arise from translation mutational towards their surface marker expression. We provide a unique method, which enables molecular characterization clinically relevant CTC subsets, as well DNA (ctDNA),...
Biomarkers for prognosis in radiotherapy-treated breast cancer patients are urgently needed and important to stratify adjuvant therapies. Recently, a role of the receptor hyaluronan-mediated motility (RHAMM) has been suggested tumor progression. Our aim was (i) investigate prognostic value RHAMM (ii) unravel its potential function radiosusceptibility cells. We demonstrate that mRNA expression biopsies is inversely correlated with grade overall survival. Radiosusceptibility vitro evaluated by...
The capture of circulating tumor cells (CTCs) is still a challenging application for microfluidic chips, as these are rare and hidden in huge background blood cells. Here, different ceiling designs regard to their efficiency CTCs model experiments more realistic conditions samples spiked with clinically relevant amount evaluated. An optimized design the platform that allows highly efficient recovery from size-based pre-enriched under obtained. Furthermore, viability captured well single cell...
Abstract BACKGROUND Genomic information can help to identify colorectal tumors with high and low metastatic potential, thereby improving prediction of benefit local and/or systemic treatment. Here we investigated chromosomal aberrations in relation the different stages cascade: dissemination tumor cells into mesenteric vein, outgrowth liver, intravasation peripheral blood circulation, development further distant metastasis. METHODS Peripheral from cancer patients (n = 72) were for...
Among emerging circulating biomarkers, miRNA has the potential to detect lung cancer and follow course of disease. However, analysis deserves further standardization before implementation into clinical trials or practice. Here, we performed international ring experiments explore (pre)-analytical factors relevant outcome blood tests in context EU network CANCER-ID. Cell-free (cfmiRNA) extracellular vesicle-derived (EVmiRNA) were extracted using miRNeasy Serum/Plasma Advanced, ExoRNeasy Maxi...
Here, we report on the outcome of 2nd International Danube Symposium advanced biomarker development that was held in Vienna, Austria, early 2018. During meeting, cross-speciality participants assessed critical aspects non-invasive, quantitative view need to expand our understanding disease mechanisms and definition appropriate strategies both for molecular diagnostics personalised therapies. More specifically, panelists addressed main topics, including current status characterisation by...
Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI certain tumor types, other types the results may be incorrect due to differences loci pattern. Here, we report case of a patient with pancreatic adenocarcinoma, confirmed by two independent next-generation sequencing tests, but not methods, who had progression on pembrolizumab. Comparison patient's patterns MSI+ colorectal adenocarcinoma samples showed lower fraction unstable loci, low...
Abstract BACKGROUND. Anti-cancer treatment failure is caused by the genetic and phenotypic heterogeneous properties of disease. Early dissemination circulating tumor cells (CTCs) into blood circulation cancer patients allows for parallel evolution primary metastases. This study investigated genomic make-up CTCs originating from metastasis as a so called “liquid biopsy” compared these with different clones archived autologous on single cell level. METHODS. From two breast patients, individual...
Abnormal methylation of the CDH1, RASSF1A, MLH1, N33, and DAPK genes was studied in intraoperative specimens gastric carcinomas adjacent nontumor tissues from 47 patients with cancer. For comparison, these examined 25 mucosa obtained by endoscopic biopsy esophageal cancer or burn. A surgical material comprising 3-5 tissue samples each patient a definitive procedure. The N33 CDH1 were methylated tumor significantly more frequently than RASSF1A MLH1 (p < 0.01). often detectable all segments...
Liquid biopsy is defined as molecular analysis of rare cells or cell-free nucleic acids circulating in blood other biofluids. The concept liquid aims at closely monitoring the status a disease treatment efficacy simple, fast, cost efficient way and any point time with minimal risk burden for patient. It has been suggested that most reproducible approach to investigate "liquid" mRNAs would be focus on extracellular vesicle (EV)-transcripts rather than mRNAs, former are well protected from...
Abstract Liquid biopsy is defined as molecular analysis of rare cells or cell-free nucleic acids circulating in blood other biofluids. The concept liquid aims at closely monitoring the status a disease treatment efficacy simple, fast, cost efficient way and any point time with minimal risk burden for patient. It has been suggested that most reproducible approach to investigate “liquid” mRNAs would be focus on extracellular vesicle (EV)-transcripts rather than mRNAs, former are well protected...
Abstract Background: High demand for liquid biopsy tests in cancer research increases the need combined approaches that allow multimodal testing from a limited blood volume. Although crosslinking-based fixatives efficient preservation of circulating cell-free DNA (ccfDNA) profile whole blood, analysis mRNA tumor cells (CTCs) is hampered. Currently, there are no collection tubes available RNA CTCs after prolonged (&gt;48 hours) storage. In this study, we present newly developed workflow...