A5066417148- Ultrasound and Hyperthermia Applications
- Cervical Cancer and HPV Research
- Virus-based gene therapy research
- Ultrasound and Cavitation Phenomena
- Monoclonal and Polyclonal Antibodies Research
- HER2/EGFR in Cancer Research
- Molecular Biology Techniques and Applications
- Hepatitis B Virus Studies
- Connexins and lens biology
- Advanced Proteomics Techniques and Applications
- Lung Cancer Research Studies
- Heat shock proteins research
- Thermal Regulation in Medicine
- 14-3-3 protein interactions
- Bioinformatics and Genomic Networks
- Hedgehog Signaling Pathway Studies
- T-cell and Retrovirus Studies
- Immune Cell Function and Interaction
- Erythrocyte Function and Pathophysiology
- Cancer Cells and Metastasis
- Immune cells in cancer
- Receptor Mechanisms and Signaling
- Advanced Biosensing Techniques and Applications
- Gene expression and cancer classification
- Cellular transport and secretion
Heidelberg University
2011-2023
University Hospital Heidelberg
2023
German Cancer Research Center
2010-2022
DKFZ-ZMBH Alliance
2017
Delivery of drugs and macromolecules to the central nervous system (CNS) is hindered by blood-brain barrier (BBB). Several approaches have been used overcome this hindrance facilitate treatment various CNS diseases. We now present results showing that chimeric adeno-associated virus 2/1 (AAV2/1) particles containing coding region for LacZ gene are efficiently delivered into rat brain upon intravenous (IV) administration after BBB opening focused ultrasound in presence vascular acoustic...
Abstract Mutations and activation of the PI3K signaling pathway in breast cancer cells have been linked to brain metastases. However, here we describe that some metastases samples protein expression components is restricted metastatic microenvironment. In contrast therapeutic effects inhibition on cells, reaction microenvironment less understood. Therefore aimed quantify activity metastasis investigate central nervous system (CNS) First, systematically metastases, performed a prospective...
The HPV E6 oncoprotein maintains the malignant phenotype of HPV-positive cancer cells and represents an attractive therapeutic target. forms a complex with cellular E6AP ubiquitin ligase, ultimately leading to p53 degradation. recently elucidated x-ray structure HPV16 E6/E6AP showed that distinct binding pocket for E6AP. This discovery raises question whether is druggable, i. e. it provides docking site functional inhibitors. To address these issues, we performed detailed analysis...
Ultrasound-induced opening of the blood-brain barrier (BBB) is an emerging technique for targeted drug delivery to central nervous system. Gap junctions allow transfer information between adjacent cells and are responsible tissue homeostasis. We examined effect ultrasound-induced BBB on structure gap in cortical neurons, expressing Connexin 36, astrocytes, 43, after focused 1-MHz ultrasound exposure at 1.25 MPa one hemisphere together with intravenous microbubble (Optison, Oslo, Norway)...
Breast cancer is the most common in women worldwide. The tumor microenvironment contributes to progression by inducing cell dissemination from primary and metastasis. TGF β signaling involved breast specifically elevated during metastatic transformation aggressive cancer. In this study, we performed genomewide correlation analysis of TGFBR 2 expression a panel 51 lines identified that MET coregulated with . This was confirmed at protein level human tissues. Flow cytometric luminal basal‐like...
Oncogenic types of human papillomaviruses (HPVs) cause cervical cancer and other malignancies in humans. The HPV E6 oncoprotein is considered to be an attractive therapeutic target since its inhibition can lead the apoptotic cell death HPV-positive cells. type 16 (HPV16) E6-binding peptide pep11, variants thereof, induce specifically HPV16-positive Although they do not encompass LxxLL binding motif found cellular HPV16 interaction partners, such as E6AP, pep11 strongly bind by contacting...
Endosomes constitute a central layer in the regulation of growth factor signaling. We applied flow cytometry, confocal microscopy and automated image quantification to define role Caveolin1 (Cav1) epidermal (EGF) receptor (i) internalization (ii) endosomal trafficking. Antisense‐downregulation Cav1 did not affect EGF:EGFR‐complexes from plasma membrane. Instead, Cav1‐knockdown had profound effect on trafficking caused shift EGF vesicle distribution towards Rab7‐negative compartments at late...
intact BBB in histochemical sections was found to be located transfected cells of CNS.Immunohistochemistery and RTPCR quantification were done analyse the transfection vector plasmid into rat brain.
Epidermal growth factor (EGF) receptor (EGFR) overexpression is a hallmark of many cancers. EGFR endocytosis critical step in signal attenuation, raising the question how expression levels affect internalization process. Here we combined quantitative experimental and mathematical modeling approaches to investigate role level on rate internalization. Using tetramethylrhodamine-labeled EGF, established assays for quantifying EGF-triggered by both high resolution confocal microscopy flow...
Targeted therapies have shown striking success in the treatment of cancer over last years. However, their specific effects on an individual tumor appear to be varying and difficult predict. Using integrative modeling approach that combines mechanistic regression modeling, we gained insights into response mechanisms breast cells due different ligand–drug combinations. The multi-pathway model, capturing ERBB receptor signaling as well downstream MAPK PI3K pathways was calibrated time-resolved...
Protein signaling networks are crucial cornerstones in cellular responses. Deregulation causes various diseases, including cancer. One pathway that is frequently deregulated cancer the WNT pathway. It has been shown highly context-dependent and availability of receptors ligands determines downstream signaling. In order to reveal which pathways activated by a specific receptor-ligand combination, we overexpressed non-canonical receptor ROR2 human breast cell line MCF-7 stimulated it with its...
This report demonstrates a novel class of innate immune cells designated "variable immunoreceptor-expressing myeloids" (VIREMs). Using single-cell transcriptomics and genome-wide epigenetic profiling, we establish that VIREMs are myeloid unrelated to lymphocytes. We visualize the phenotype B-VIREMs capable genetically recombining expressing antibody genes, exclusive hallmark function B These cells, B-VIREMs, display monoclonal cell surface signatures regularly circulate in blood healthy...
Abstract Large number of breast cancer patients clinically classified as HER2 negative, show low/moderate levels along with other ERBB receptors. Concomitant blockade EGFR, ERBB2 and ERBB3 specific therapeutic antibodies (cetuximab, trastuzumab/pertuzumab lumretuzumab, respectively) appears a beneficial approach to improve survival who have failed previous treatment strategies. Additionally, expression has been reported trastuzumab resistance mechanism in positive subtypes.We confirmed...
Introduction ERBB family of receptors tirosine kinases (RTK) are potent drivers tumorogenesis and metastasis. In breast tumours, 70%–80% patients, although clinically not classified as HER2 positive, show low or moderate expression along with EGFR ERBB3. Concomitant blockade specific monoclonal antibodies based on proteomic profile determined by Reverse Phase Protein Array (RPPA), appears a beneficial approach to improve treatment strategies. Material methods Cancer cells lines from...