A5020369086- Glioma Diagnosis and Treatment
- Neuroinflammation and Neurodegeneration Mechanisms
- Immune cells in cancer
- Apelin-related biomedical research
- Brain Metastases and Treatment
- Meningioma and schwannoma management
- Cancer, Hypoxia, and Metabolism
- Neurogenesis and neuroplasticity mechanisms
- Lipid metabolism and disorders
- MicroRNA in disease regulation
- Chemokine receptors and signaling
- Cancer Cells and Metastasis
- Cerebrovascular and Carotid Artery Diseases
- Intracranial Aneurysms: Treatment and Complications
- Angiogenesis and VEGF in Cancer
- Neurological disorders and treatments
- Nanoparticle-Based Drug Delivery
- Adenosine and Purinergic Signaling
- Spinal Dysraphism and Malformations
- Neuroscience and Neuropharmacology Research
- Parkinson's Disease Mechanisms and Treatments
- Cancer Genomics and Diagnostics
- Moyamoya disease diagnosis and treatment
- Advanced Neuroimaging Techniques and Applications
- RNA Interference and Gene Delivery
University Hospital Schleswig-Holstein
2016-2025
University of Lübeck
2016-2025
University Medical Center
2019-2023
Kiel University
2016-2021
Charité - Universitätsmedizin Berlin
2008-2020
Heidelberg University
2019
Goethe University Frankfurt
2019
Universität Ulm
2019
Zimmer Biomet (Germany)
2019
United States Nuclear Regulatory Commission
2018
Diffuse infiltration of glioma cells into normal brain tissue is considered to be a main reason for the unfavorable outcomes patients with malignant gliomas. Invasion parenchyma facilitated by metalloprotease-mediated degradation extracellular matrix. Metalloproteases are released as inactive pro-forms and get activated upon cleavage membrane bound metalloproteases. Here, we show that type 1 metalloprotease (MT1-MMP) up-regulated in glioma-associated microglia, but not cells. Overexpression...
Malignant glioma belong to the most aggressive neoplasms in humans with no successful treatment available. Patients suffering from glioblastoma multiforme (GBM), highest-grade glioma, have an average survival time of only around one year after diagnosis. Both microglia and peripheral macrophages/monocytes accumulate within but fail exert effective anti-tumor activity even support tumor growth. Here we use microarray analysis compare expression profiles glioma-associated microglia/macrophages...
Gliomas represent the most frequent type of human brain tumor, and their strong invasiveness is a significant clinical problem. Microglia, immunocompetent cells brain, contribute significantly to tumor are potential interaction partners glioma cells. We studied impact presence microglia on cell invasion in cultured slices. To selectively deplete microglia, slices were treated with clodronate-filled liposomes. When injected into devoid endogenous tumors was decreased as compared controls....
Neural precursor cells contribute to adult neurogenesis and limited attempts of brain repair after injury. Here we report that in a murine experimental glioblastoma model, endogenous neural precursors migrate from the subventricular zone toward tumor surround it. The association with syngenic grafts was observed, injecting red fluorescent protein-labeled G261 into caudate-putamen transgenic mice, which express green protein under promoter for nestin (nestin-GFP). Fourteen days inoculation,...
Abstract Statins [3‐hydroxy‐3‐methylglutaryl‐coenzyme A (HMG‐CoA) reductase inhibitors] exert cholesterol‐independent pleiotropic effects that include anti‐thrombotic, anti‐inflammatory, and anti‐oxidative properties. Here, we examined direct protective of atorvastatin on neurones in different cell damage models vitro . Primary cortical were pre‐treated with then exposed to (i) glutamate, (ii) oxygen–glucose deprivation or (iii) several apoptosis‐inducing compounds. Atorvastatin...
Accumulation and infiltration of microglia/brain macrophages around into glioma tissue promote tumor invasion expansion. One tumor-promoting mechanism is upregulation membrane type 1 matrix metalloprotease (MT1-MMP), which promotes the degradation extracellular matrix. MT1-MMP induced by soluble factors released cells activating microglial Toll-like receptor 2 (TLR2). Versican identified proteomics was silenced in short interference RNA hairpin approaches studied vitro after injection mouse...
Glioblastomas are the most aggressive primary brain tumors in humans. Microglia/brain macrophage accumulation and around tumor correlates with malignancy poor clinical prognosis of these tumors. We have previously shown that microglia promote glioma expansion through upregulation membrane type 1 matrix metalloprotease (MT1-MMP). This depends on signaling via Toll-like receptor (TLR) adaptor molecule myeloid differentiation response gene 88 (MyD88).Using vitro, ex vivo, vivo techniques, we...
<h3>BACKGROUND AND PURPOSE:</h3> Recent studies have suggested that wall enhancement of unruptured intracranial aneurysms in high-resolution MR imaging might serve as an biomarker for higher risk rupture. Histologic revealed a possible association among inflammatory processes, degeneration, and destabilization the aneurysm preceding Understanding histologic condition underlying could be important step toward assessing value this method stratification. We present our observations vessel...
The invasiveness of malignant gliomas is one the major obstacles in glioma therapy and reason for poor survival patients. Glioma cells infiltrate into brain parenchyma thereby escape surgical resection. associated microglia/macrophages support infiltration by increased expression activation extracellular matrix degrading proteases such as metalloprotease (MMP) 2, MMP9 membrane‐type 1 MMP. In this work we demonstrate that, predominantly expressed mouse human tissue but not cells. Supernatant...
Glioblastoma (GBM) is the most aggressive brain tumor in adults. It strongly infiltrated by microglia and peripheral monocytes that support growth. In present study we used RNA sequencing to compare expression profile of CD11b(+) human glioblastoma-associated microglia/monocytes (hGAMs) isolated from non-tumor samples. Hierarchical clustering principal component analysis showed a clear separation two sample groups identified 334 significantly regulated genes hGAMs. comparison control hGAMs...
Abstract Background Molecular brain tumor diagnosis is usually dependent on tissue biopsies or resections. This can pose several risks associated with anesthesia neurosurgery, especially for lesions in the stem other difficult-to-reach anatomical sites. Apart from initial diagnosis, progression, recurrence, acquisition of novel genetic alterations only be proven by re-biopsies. Methods We employed Nanopore sequencing cell-free DNA (cfDNA) cerebrospinal fluid (CSF) and analyzed copy number...
Abstract Although the intraoperative molecular diagnosis of approximately 100 known brain tumor entities described to date has been a goal neuropathology for past decade, achieving this within clinically relevant timeframe under 1 h after biopsy collection remains elusive. Advances in third-generation sequencing have brought closer, but established machine learning techniques rely on computationally intensive methods, making them impractical live diagnostic workflows clinical applications....
The invasion of tumour cells into brain tissue is a pathologic hallmark WHO grades II-IV gliomas and contributes significantly to the failure current therapeutic treatments. Activated microglial are abundant in tumours may support invasiveness. We have previously demonstrated that cyclosporin A (CsA) can affect growth glioma vitro by inhibiting signalling pathways, which essential for proliferation In this work, we demonstrate migration EGFP-transfected glioblastoma organotypic slices was...
Sorting protein-related receptor with A-type repeats (SORLA) is a major risk factor in cellular processes leading to Alzheimer's disease (AD). It acts as sorting for the amyloid precursor protein (APP) that regulates intracellular trafficking and processing into amyloidogenic-β peptides (Aβ). Overexpression of SORLA neurons reduces while inactivation gene expression (as knock-out mouse models) accelerates amyloidogenic senile plaque formation. The current study aimed at identifying molecular...
Glioblastoma cells with stem-like properties control brain tumour growth and recurrence. Here, we show that endogenous neural precursor perform an anti-tumour response by specifically targeting cells. In vitro, predominantly express bone morphogenetic protein-7; protein-7 is constitutively released from neurospheres induces canonical protein signalling in glioblastoma Exposure of human murine to neurosphere-derived stem cell differentiation, attenuates marker expression reduces self-renewal...
Glioblastoma is the most common and lethal primary brain tumor. Tumor initiation recurrence are likely caused by a sub-population of glioblastoma stem cells, which may derive from mutated neural precursor cells. Since CD133 cell marker for both normal glioblastoma, to better understand formation recurrence, we looked dys-regulated microRNAs in human CD133+ cells as opposed isolated brain. Using FACS sorting low-passage samples followed microRNA microarray analysis, found 43 that were three...
Peripheral macrophages and resident microglia constitute the dominant glioma-infiltrating cells. The tumor induces an immunosuppressive tumor-supportive phenotype in these glioma-associated microglia/brain (GAMs). A subpopulation of glioma cells acts as stem (GSCs). We explored interaction between GSCs GAMs. Using CD133 a marker stemness, we enriched for or deprived mouse cell line GL261 by fluorescence-activated sorting (FACS). Over same period time, 100 CD133+ had capacity to form...
AT101, the R-(-)-enantiomer of cottonseed-derived polyphenol gossypol, is a promising drug in glioblastoma multiforme (GBM) therapy due to its ability trigger autophagic cell death but also facilitate apoptosis tumor cells. It does have some limitations such as poor solubility water-based media and consequent low bioavailability, which affect response rate during treatment. To overcome this drawback improve anti-cancer potential use cubosome-based formulation for AT101 delivery has been...
Abstract Antiangiogenic therapy of glioblastoma (GBM) with bevacizumab, a VEGFA-blocking antibody, may accelerate tumor cell invasion and induce alternative angiogenic pathways. Here we investigate the roles proangiogenic apelin receptor APLNR its cognate ligand in VEGFA/VEGFR2 antiangiogenic against distinct subtypes GBM. In proneural GBM, levels were downregulated by VEGFA or VEGFR2 blockade. A central role for apelin/APLNR controlling GBM vascularization was corroborated serial...