A5086640516- Systemic Sclerosis and Related Diseases
- Immune cells in cancer
- Angiogenesis and VEGF in Cancer
- Cardiac Fibrosis and Remodeling
- Muscle Physiology and Disorders
- Pulmonary Hypertension Research and Treatments
- Phagocytosis and Immune Regulation
- Cancer, Hypoxia, and Metabolism
- Cancer Research and Treatments
- Cardiac Ischemia and Reperfusion
- Signaling Pathways in Disease
- Connective Tissue Growth Factor Research
- Cell Adhesion Molecules Research
- Neuroblastoma Research and Treatments
- Fibroblast Growth Factor Research
- Venous Thromboembolism Diagnosis and Management
- Nitric Oxide and Endothelin Effects
- Tissue Engineering and Regenerative Medicine
- Transplantation: Methods and Outcomes
- Cancer Cells and Metastasis
- Protein Kinase Regulation and GTPase Signaling
- Cardiomyopathy and Myosin Studies
- Cytokine Signaling Pathways and Interactions
- Chemokine receptors and signaling
- Protease and Inhibitor Mechanisms
Medical University of Vienna
2015-2025
University of Vienna
2000-2024
University College London
1997-2024
Comprehensive Cancer Center Vienna
2015-2023
The Royal Free Hospital
1997-2020
University Children's Hospital Zurich
2019
Baker Heart and Diabetes Institute
2019
Charité - Universitätsmedizin Berlin
2019
Universitätsklinikum St. Pölten
2019
Zero to Three
2009
Abstract Colony-stimulating factor (CSF)-1 is the primary regulator of tissue macrophage production. CSF-1 expression correlated with poor prognosis in breast cancer and believed to enhance mammary tumor progression metastasis through recruitment regulation tumor-associated macrophages. Macrophages produce matrix metalloproteases (MMPs) vascular endothelial growth factor, which are crucial for invasion angiogenesis. Given important role CSF-1, we hypothesized that blockade or receptor (the...
Overexpression of colony-stimulating factor-1 (CSF-1) and its receptor in breast cancer is correlated with poor prognosis. Based on the hypothesis that blockade CSF-1 would be beneficial treatment, we developed a murinized, polyethylene glycol-linked antigen-binding fragment (Fab) against mouse (host) (anti-CSF-1 Fab). Mice bearing human, chemoresistant MCF-7 xenografts were treated combination chemotherapy (CMF: cyclophosphamide, methotrexate, 5-fluorouracil; cycled twice i.p.), anti-CSF-1...
The Raf-1 kinase plays a key role in relaying proliferation signals elicited by mitogens or oncogenes. is regulated complex and incompletely understood mechanisms including phosphorylation. A number of studies have indicated that phosphorylation serines 259 621 can inhibit the kinase. We show both are hypophosphorylated during early mitogenic stimulation hypophosphorylation correlates with peak activation. Concentrations okadaic acid selectively protein phosphatase 2A (PP2A) induce these...
Cardiomyopathy (CM) comprises a heterogeneous group of diseases, including ischemic (ICM) and dilative (DCM) forms. The pathogenesis primary DCM is not clearly understood. Recent studies in mice show that vascular endothelial growth factor (VEGF) involved ICM. Whether VEGF plays role human CM unknown. We examined the mRNA protein expression its receptors hearts patients with end-stage ICM healthy individuals using real-time polymerase chain reaction Western blotting. Number capillaries, area...
Abstract The interplay between malignant and stromal cells is essential in tumorigenesis. We have previously shown that colony-stimulating factor (CSF)-1, matrix metalloprotease (MMP)-2, vascular endothelial growth (VEGF)-A production by enhanced CSF-1–negative SW620 colon cancer cells. In the present study, mechanisms which up-regulate host factors to promote tumorigenesis were investigated. Profiling of tumor cell cytokine expression xenografts nude mice showed increased human necrosis...
Deregulated Rho GTPases Rac1 and Cdc42 have been discovered in various tumors, including prostate Rac protein expression significantly increases cancer. The pathways promote the uncontrolled proliferation, invasion metastatic properties of human cancer cells. We synthesized novel compound AZA1 based on structural information known inhibitor NSC23766. In current study we investigated effects inhibition these by tumorigenicity performing preclinical studies using a xenograft mouse model...
Mitogenic stimulation of Raf-1 is a complex yet incompletely understood process involving membrane relocalization and phosphorylation activating residues. We recently reported that Raf-1-associated protein phosphatase 2A contributes to kinase activation, an effect mediated via Ser-259 Raf-1. Here, we show mitogens stimulate dephosphorylation Raf-1/protein association concomitantly with accumulation activation Blocking inhibits the two latter events, but it does not prevent S259A mutant,...
The molecular mechanisms of tumor-host interactions that render neuroblastoma (NB) cells highly invasive are unclear. Cancer upregulate host stromal cell colony-stimulating factor-1 (CSF-1) production to recruit tumor-associated macrophages (TAMs) and accelerate tumor growth by affecting extracellular matrix remodeling angiogenesis. By coculturing NB with in vitro, we showed the importance CSF-1 expression for macrophage recruitment cells. To examine this interaction vivo, mice bearing human...
Rho GTPases play important roles in cytoskeleton organization, cell cycle progression and are key regulators of tumor progression. Strategies to modulate increased GTPase activities during cancer could have therapeutic potential.We report here the characterization a Cdc42-selective small-molecule inhibitor AZA197 for treatment colon that was developed based on structural information known from previously compounds affecting activation. We investigated effects RhoA, Rac1 Cdc42 associated...
Abstract Duchenne muscular dystrophy (DMD), a severe muscle disease caused by mutations in the gene encoding for intracellular protein dystrophin, is associated with impaired cardiac function and arrhythmias. A causative factor complications dystrophic heart abnormal calcium (Ca) handling ventricular cardiomyocytes, restoration of normal Ca homeostasis has emerged as therapeutic strategy. Here, we used rodent model DMD, dystrophin-deficient DMD mdx rat, to test following hypothesis: chronic...
Abstract BACKGROUND Recent studies show that vascular endothelial growth factor (VEGF) and its receptors Flt‐1 KDR, a series of other angiogenic molecules, are upregulated in advanced but not low stage human neuroblastoma. Neuropilin‐1 2 (NRP) novel specific VEGF 165 , whose role is unknown METHODS Tissue biopsies 37 children with Stage I‐IV neuroblastoma were obtained, as well 7 normal adrenals controls. The mRNA expression Flt‐1, NRP1, NRP2 was evaluated by real‐time reverse transcripton...
Left ventricular (LV) hypertrophy is characterized by cardiomyocyte and interstitial fibrosis ultimately leading to increased myocardial stiffness reduced contractility. There substantial evidence that the altered expression of matrix metalloproteinases (MMP) Tenascin-C (TN-C) are associated with progression adverse LV remodeling. However, role TN-C in development because chronic pressure overload as well regulatory on MMPs remains unknown.In a knockout mouse model TN-C, we investigated...
Home blood pressure (HBP) monitoring plays an increasingly important role in the diagnosis and treatment of hypertension. We evaluated independent value HBP compared with ambulatory (ABP) office (OBP) prediction cardiovascular end-organ damage normotensive subjects untreated patients mild One hundred sixty-three underwent measurements OBP, HBP, ABP, echocardiography. A physician using a mercury-column sphygmomanometer performed three OBP measurements. The ABP was recorded noninvasive monitor...
Interleukin-34 (IL-34) is a ligand for the CSF-1R and has also two additional receptors, PTPRZ1 syndecan-1. IL-34 plays role in innate immunity, inflammation, cancer. However, of breast cancer still ill-defined. We analyzed mRNA expression cell lines patients applied established computational approaches (CIBERSORT, ESTIMATE, TIMER, TCIA), to analyze gene data from The Cancer Genome Atlas (TCGA). Expression was associated with favorable prognosis luminal HER2 but not basal patients. Gene...
Besides skeletal muscle abnormalities, Duchenne muscular dystrophy (DMD) patients present with dilated cardiomyopathy development, which considerably contributes to morbidity and mortality. Because the mechanisms responsible for cardiac complications in context of DMD are largely unknown, evidence-based therapy approaches still lacking. This has increased need basic research efforts into animal models DMD. Here, we characterized detail cardiovascular abnormalities Dmdmdx rats, aim...
Frizzled2 (FZD2) is a receptor for Wnts and may activate both canonical non-canonical Wnt signaling pathways in cancer. However, no studies have reported an association between FZD2 high-risk NB so far. Here we report that are critical to growth MYCN-single copy SK-N-AS MYCN-amplified SK-N-DZ cells. We demonstrate stimulation of by Wnt3a Wnt5a regulates β-catenin-dependent -independent factors. blockade suppressed activity increased phosphorylation PKC, AKT ERK vitro, consistent with...
Chronic kidney disease is a global health problem affecting 10% to 12% of the population. Uremic cardiomyopathy often characterized by left ventricular hypertrophy, fibrosis, and diastolic dysfunction. Dysregulation neuregulin-1β signaling in heart known contributor failure. The systemically administered recombinant human for 10 days our 5/6 nephrectomy-induced model chronic alleviated progression uremic dysfunction type 4 cardiorenal syndrome. currently presented positive preclinical data...
Treatment of Escherichia coli with diazaborine strongly induces the synthesis a 28 kDa protein which is associated cytoplasmic membrane. The partial amino acid sequence proved that this identical to phage shock PspA. kinetics expression pspA gene were determined in an E. strain carried pspA-lacZ fusion chromosome. PspA independent growth phase. It is, however, induced when fatty biosynthesis inhibited by or cerulenin. either compound also causes dose-dependent inhibition phospholipid whose...
Background. Vascular endothelial growth factor (VEGF) is a potent cell and permeability factor, expressed in the lung. Overexpression of VEGF associated with increased vascular early stage acute lung injury mice. The role various forms transplantation-induced not well understood. Methods. mRNA protein expression was measured biopsies preserved donor grafts as control biopsies, using real-time reverse transcriptase–polymerase chain reaction Western blot analysis. tissue also evaluated by...
The cross-talk between vascular endothelial growth factor (VEGF)-A, angiopoietin (Ang), and VE-cadherin coregulates cell (EC) survival. Cardiac expression of VEGF-A but not its receptor KDR is blunted in dilated cardiomyopathy (DCM). Whether VE-cadherin/Ang function affected DCM unknown.The myocardial VE-cadherin/beta-catenin, Ang-1, Ang-2, their Tie-2 was examined DCM, ischemic (ICM), control subjects through the use real-time RT-PCR, Western blotting, immunocytochemistry. EC degeneration...
AimsSkeletal myoblasts are used in repair of ischaemic myocardium. However, a large fraction grafted degenerate upon engraftment. Colony-stimulating factor-1 (CSF-1) accelerates myoblast proliferation and angiogenesis. We hypothesized that CSF-1 overexpression improves survival cardiac function ischaemia-induced heart failure.