A5083166298- Cancer Cells and Metastasis
- Cancer Immunotherapy and Biomarkers
- Neurogenesis and neuroplasticity mechanisms
- Neuroendocrine Tumor Research Advances
- Cancer Genomics and Diagnostics
- Prostate Cancer Treatment and Research
- Glycosylation and Glycoproteins Research
- Nerve injury and regeneration
- Neuroinflammation and Neurodegeneration Mechanisms
- Single-cell and spatial transcriptomics
- Renal and related cancers
- Monoclonal and Polyclonal Antibodies Research
- Cancer and Skin Lesions
- Ovarian cancer diagnosis and treatment
- Cancer Research and Treatments
- Immunotherapy and Immune Responses
- HER2/EGFR in Cancer Research
- Immune cells in cancer
- Renal cell carcinoma treatment
- Pluripotent Stem Cells Research
- Molecular Biology Techniques and Applications
- Alzheimer's disease research and treatments
- Cancer-related gene regulation
- Cancer, Hypoxia, and Metabolism
- Genetic factors in colorectal cancer
Universität Hamburg
2015-2024
University Medical Center Hamburg-Eppendorf
2015-2024
University at Buffalo, State University of New York
2022
Cleveland Clinic
2022
Klinikum Itzehoe
2021
Taipei Institute of Pathology
2021
National University of Singapore
2017
Munich Cluster for Systems Neurology
2017
Technical University of Munich
2017
Kiel University
2017
Multi-protein complexes called inflammasomes have recently been identified and shown to contribute cell death in tissue injury. Intravenous immunoglobulin (IVIg) is an FDA-approved therapeutic modality used for various inflammatory diseases. The objective of this study investigate dynamic responses the NLRP1 NLRP3 stroke determine whether can be targeted with IVIg intervention. Primary cortical neurons were subjected glucose deprivation (GD), oxygen–glucose (OGD) or simulated...
The metalloproteinase and major amyloid precursor protein (APP) α-secretase candidate ADAM10 is responsible for the shedding of proteins important brain development, such as cadherins, ephrins, Notch receptors. Adam10 −/− mice die at embryonic day 9.5, due to defects in development somites vasculogenesis. To investigate function brain, we generated conditional knock-out (cKO) using a Nestin-Cre promotor, limiting inactivation neural progenitor cells (NPCs) NPC-derived neurons glial cells....
Stroke represents one of the leading causes death and disability in Western countries, but despite intense research, only few options exist for treatment stroke-related infarction brain tissue. In experimental stroke, cell therapy can partly reverse some behavioural deficits. However, underlying mechanisms have remained unknown as most studies revealed little, if any, evidence neuronal replacement observed improvements appeared to be related rather a graft-derived induction positive response...
Background Mice lacking the type I interferon receptor (IFNAR−/− mice) reproduce relevant aspects of Crimean-Congo hemorrhagic fever (CCHF) in humans, including liver damage. We aimed at characterizing pathology CCHF virus-infected IFNAR−/− mice by immunohistochemistry and employed model to evaluate antiviral efficacy ribavirin, arbidol, T-705 against virus. Methodology/Principal Findings died 2–6 days post infection with elevated aminotransferase levels high virus titers blood organs. Main...
Background Chemotherapy of glioblastoma is largely ineffective as the blood-brain barrier (BBB) prevents entry most anticancer agents into brain. For an efficient treatment glioblastomas it necessary to deliver anti-cancer drugs across intact BBB. Poly(lactic-co-glycolic acid) (PLGA) nanoparticles coated with poloxamer 188 hold great promise drug carriers for brain delivery after their intravenous injection. In present study anti-tumour efficacy surfactant-coated doxorubicin-loaded PLGA...
Glioblastomas are the most common and deadly primary brain tumors. Here, we evaluated chemotherapeutic effect of natural polyphenol curcumin on glioma cells in vitro vivo using an immunocompetent orthotopic mouse model.Curcumin's effects proliferation, cell cycle, migration, invasion, JAK/STAT3 signaling, STAT3 target gene expression, STAT3C rescue experiments were determined murine lines vitro. Therapeutic tumor-bearing mice fed a Western-type diet fortified with (0.05%, w/w) control...
The metalloproteinase ADAM10 is of importance for Notch-dependent cortical brain development. protease tightly linked with α-secretase activity toward the amyloid precursor protein (APP) substrate. Increasing suggested as a therapy to prevent production neurotoxic β (Aβ) peptide in Alzheimer′s disease. To investigate function postnatal brain, we generated <i>Adam10</i> conditional knock-out (A10cKO) mice using CaMKIIα-Cre deleter strain. lack expression was evident cortex leading reduced...
Abstract Although clinically relevant, the detection rates of EpCAM positive CTCs in non-small cell lung cancer (NSCLC) are surprisingly low. To find new informative markers for CTC NSCLC, expression EGFR and HER3 was first analyzed NSCLC tissue (n = 148). A staining observed 52.3% 82.7% primary tumors, 62.7% 91.2% brain metastases, respectively. Only 3.0% metastases samples were negative both proteins, indicating that majority express these ERBB which therefore chosen enrichment using...
Inflammatory mechanisms can exacerbate ischemic tissue damage and worsen clinical outcome in patients with stroke. Both αβ γδ T cells are established mediators of stroke, the role dendritic (DCs) inducing early events cell activation differentiation stroke is not well understood.In a murine model experimental we defined immune phenotype infiltrating DC subsets based on flow cytometry surface markers, expression ontogenetic cytokine levels. We used conditional depletion, bone marrow chimeric...
Mesothelin (MSLN) represents an attractive molecule for targeted cancer therapies. To identify tumors that might benefit from such therapies, tissue microarrays including 15,050 122 different tumor types and 76 healthy organs were analyzed MSLN expression by immunohistochemistry. Sixty-six (54%) showed at least occasional weak staining, 50 (41%) with one strongly positive sample. Highest prevalence of positivity had ovarian carcinomas (serous 97%, clear cell 83%, endometrioid 77%, mucinous...
Trophoblast cell surface antigen 2 (TROP2) is the target of sacituzumab govitecan, an antibody-drug conjugate approved for treatment triple negative breast cancer and urothelial carcinoma.A tissue microarray containing 18,563 samples from 150 different tumor types subtypes as well 608 76 normal was analyzed by TROP2 immunohistochemistry.TROP2 positivity found in 109 categories, including squamous carcinomas various origins, urothelial, breast, prostate, pancreatic, ovarian cancers (>95%...
Introduction: GATA3 is a transcription factor involved in epithelial cell differentiation. immunostaining used as diagnostic marker for breast and urothelial cancer but can also occur other neoplasms. Methods: To evaluate normal tumor tissues, tissue microarray containing 16,557 samples from 131 different types subtypes 608 of 76 was analyzed by immunohistochemistry. Results: positivity found 69 including 23 (18%) with at least one strongly positive tumor. Highest rates occurred noninvasive...
The cellular prion protein (PrPC) fulfils several yet not completely understood physiological functions. Apart from these functions, it has the ability to misfold into a pathogenic scrapie form (PrPSc) leading fatal transmissible spongiform encephalopathies. Proteolytic processing of PrPC generates N- and C-terminal fragments which play crucial roles both in pathophysiology diseases transducing functions PrPC. A-disintegrin-and-metalloproteinase 10 (ADAM10) been proposed by cell culture...
Active or passive immunization of Alzheimer's disease (AD) patients leads to targeting beta-amyloid plaques by immunoglobulins (IgG) and their subsequent removal microglia. Here, we investigate whether naturally occurring autoantibodies contribute plaque in nonimmunized AD patients.We generated an tissue microarray with 2,325 specimens from 3 defined central nervous system regions 48 age-matched control patients. Absolute quantification beta-amyloid, plaque-bound IgG, phagocytic, resting,...
Blood-brain-barrier (BBB) breakdown and cerebral edema result from postischemic inflammation contribute to mortality morbidity after ischemic stroke. A functional role for the carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in regulation of reperfusion injury has not yet been demonstrated.We sought identify characterize relevance CEACAM1-expressing inflammatory cells BBB outcome stroke Ceacam1(-/-) wild-type mice.Focal ischemia was induced by temporary occlusion middle...
Mutations of CCM3/PDCD10 cause 10-15% hereditary cerebral cavernous malformations. The phenotypic characterization CCM3-mutated patients has been hampered by the limited number harboring a mutation in this gene. This is first report on molecular and clinical features large cohort CCM3 patients. Molecular screening for point mutations deletions was used to identify 54 index Age at referral onset, type inaugural events presence extra-axial lesions were investigated these 22 their mutated...
Brain injury during stroke results in oxidative stress and the release of factors that include extracellular Ca(2+), hydrogen peroxide, adenosine diphosphate ribose, nicotinic acid adenine dinucleotide phosphate. These alterations milieu change activity transient receptor potential melastatin subfamily member 2 (TRPM2), a nonselective cation channel expressed central nervous system immune system. Our goal was to evaluate contribution TRPM2 tissue damage after stroke.In accordance with...
The prion protein (PrPC) is highly expressed in the nervous system and critically involved diseases where it misfolds into pathogenic PrPSc. Moreover, has been suggested as a receptor mediating neurotoxicity common neurodegenerative proteinopathies such Alzheimer's disease. PrPC shed at plasma membrane by metalloprotease ADAM10, yet impact of this on disease remains enigmatic. Employing conditional knockout mice, we show that depletion ADAM10 forebrain neurons leads to posttranslational...
Abstract Background Tumor protein 63 (p63) is a transcription factor of the p53 gene family involved in differentiation several tissues including squamous epithelium. p63 immunohistochemistry broadly used for tumor classification but published data on its expression cancer conflicting. Methods To comprehensively catalogue expression, tissue microarrays (TMAs) containing 12,620 samples from 115 entities and 76 normal types were analyzed. Results was seen various epithelium urothelium. At...
Abstract Background Cytokeratin 18 (CK18) is an intermediate filament protein of the cytokeratin acidic type I group and primarily expressed in single-layered or “simple” epithelial tissues carcinomas different origin. Methods To systematically determine CK18 expression normal cancerous tissues, 11,952 tumor samples from 115 types subtypes (including carcinomas, mesenchymal biphasic tumors) as well 608 76 tissue were analyzed by immunohistochemistry a microarray format. Results was cells...
Abstract Background The E-Cadherin gene ( CDH1, Cadherin 1 ), located at 16q22.1 encodes for a calcium-dependent membranous glycoprotein with an important role in cellular adhesion and polarity maintenance. Methods To systematically determine protein expression normal cancerous tissues, 14,637 tumor samples from 112 different types subtypes as well 608 of 76 tissue were analyzed by immunohistochemistry microarray format. Results was strongly expressed epithelial cells most organs. From 77...
Expansion of CD8+ cytotoxic Tlymphocytes is a prerequisite for anti-cancer immune activity and has gained interest in the era checkpoint therapy.To understand T cell dynamics tumor microenvironment, we used multiplex fluorescence immunohistochemistry to quantitate proliferation (Ki67 co-expression) tissue microarrays from 1107 colorectal, 642 renal cell, 1066 breast, 375 ovarian, 451 pancreatic 347 gastric cancer samples.The density percentage proliferating (Ki67+) cells were both highly...