317 search results for “in vivo insertional mutagenesis” in the Public website
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Using insertional mutagenesis to identify breast cancer drivers and therapy resistance genes in mice
In this thesis, we used genetically engineered mouse models to identify genes and pathways that are involved in ILC formation and in the development of resistance to FGFR-targeted therapy.
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Drug-target binding kinetics in vivo
A next, general pharmacological problem to be tackled is how drug-target binding kinetics in vivo, affects target occupancy as an important indicator of the time-course of drug effects.
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Regulation of actomyosin contraction as a driving force of invasive lobular breast cancer
In this thesis, we used genetically engineered mouse models and a variety of cell-culture based assays to identify genes and pathways that are involved in the development and treatment of invasive lobular carcinoma (ILC).
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In vivo modelling of Ewing sarcoma in zebrafish
Promotores: Prof.dr. P.C.W. Hogendoorn & Prof.dr. H.P. Spaink, Co-promotor: Dr. B.E. Snaar-Jagalska
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Spatial (3-D) CNS drug distribution in vivo
Another research line is the development of a spatial CNS drug distribution model, by ultimately including the 3-dimensional anatomical organization of the CNS.
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In vivo tracking and biodistribution of protein aggregates
Therapeutic proteins have revolutionized the treatment of many severe diseases like multiple sclerosis, haemophilia, diabetes and many more. Unfortunately, even recombinant proteins with structures (almost) identical to those of their endogenous counterparts often induce the formation of anti drug antibodies…
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RESTORING T-CELL HOMEOSTASIS BY IN VIVO MANIPULATION OF DENDRITIC CELLS
The loss of T-cell homeostasis and tolerance towards self-antigens is the underlying cause of autoimmune and inflammatory diseases like atherosclerosis, rheumatoid arthritis or type I diabetes. Traditionally, the treatment of these diseases consisted on systemic immune suppression, which can entail…
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Squaramide-based supramolecular polymers: from self-assembly to in vivo application
The aim of this thesis is to develop and study a robust and adaptable scaffold for supramolecular polymer self-assembly in water.
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In vitro and in vivo delivery of functionalized nanoparticles via coiled-coil interactions
Promotor: A. Kros, Co-promotor: R.R.C.L. Olsthoorn
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Two-photon multifocal microscopy for in vivo single-molecule and single-particle imaging
In this thesis we investigated the ability of two-photon multifocal microscopy for single-molecule microscopy in live cells and organisms.
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In vivo fluorescence imaging of IgG1 aggregates after subcutaneous and intravenous injection in mice
PURPOSE: To monitor the biodistribution of IgG1 aggregates upon subcutaneous (SC) and intravenous (IV) administration in mice and measure their propensity to stimulate an early immune response.
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binding kinetics as determinant of the time course of drug action in vivo
Drug-target binding kinetics determine the time course of the central event in pharmacotherapy: Drug-target interaction.
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Broad-Spectrum Profiling of Retaining β-Exoglucosidases In Situ and In Vivo
A high-end label: Cyclophellitol aziridine-type activity-based probes allow for ultra-sensitive visualization of mammalian β-glucosidases (GBA1, GBA2, GBA3, and LPH) as well as several non-mammalian β-glucosidases (see picture). These probes offer new ways to study β-exoglucosidases, and configurational…
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receptor allosteric modulator induces an anti-inflammatory effect: in vivo studies and molecular mechanism of action
Source: Mediators Inflamm (2014)
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In vitro and in vivo evaluation of synergistic and opposing effects of Chinese herbal medicine and natural compounds on immuno-modulation.
Can we link multiple components from herbal extracts with their biological activities?
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Specificity and side-effects of mutagenesis by CRISPR/Cas9 -induced breaks in plants
Do large deletions represent a risk during CRISP/CAS9-mediated genome editing in plants?
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CRISPR Cas-induced targeted mutagenesis with Agrobacterium mediated protein delivery
The RNA guided endonuclease based on the CRISPR/Cas system of Streptococcus pyogenus is a potent new tool for genome engineering in plants.
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A novel formulation for skin barrier repair : from ex vivo assessment towards clinical studies
The stratum corneum is the outermost skin layer and consists of dead cells embedded in a lipid matrix.
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Impact-Insertion Applicator Improves Reliability of Skin Penetration by Solid Microneedle Arrays
Source: The AAPS journal, Volume 16, Issue 4, pp. 681-684 (2014)
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An ex vivo human skin model for studying skin barrier repair
In the studies described in this study, we introduce a novel ex vivo human skin barrier repair model. To develop this, we removed the upper layer of the skin, the stratum corneum (SC) by a reproducible cyanoacrylate stripping technique.
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Parameter optimization toward optimal microneedle-based dermal vaccination
Microneedle-based vaccination has several advantages over vaccination by using conventional hypodermic needles.
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Scanning mutagenesis in a yeast system delineates the role of the NPxxY(x)(5,6)F motif and helix 8 of the adenosine A(2B) receptor in G protein
Source: Biochem Pharmacol, Volume 95, Issue 4, pp. 290-300 (2015)
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Agrobacterium-mediated protein therapy for genome editing
Is translocation of nucleases possible via Agrobacterium T4SS and is it efficient enough for mutagenesis?
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Creating a brain atlas
Researchers have been working for centuries in mapping the human brain. But in the year 2017 some brain structures remain still not well mapped, especially those located at the brainstem. In this paper, we quantified the test–retest reliability of imaging the brainstem nucleus locus coeruleus in vivo…
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Precision modeling of breast cancer in the CRISPR era
The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.
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CAM-PaC
The overall aim of CAM-PaC is to contribute to solving the socioeconomic and health challenges of PDAC by an integrative and systematic functional analysis of pancreatic cancer candidate genes. CAM-PaC will develop novel cellular and animal models, as well as novel strategies to analyse and integrate…
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Evaluation of the zebrafish embryo as an alternative model for hepatotoxicity testing
Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis
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Predictive pharmacology
The aim of this research area is to be able to predict human drug response on the basis of mathematical models that are developed using preclinical experiments and prior knowledge.
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Towards improved drug action : target binding kinetics and functional efficacy at the mGlu2 receptor
During the course of drug discovery translational steps are made.
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Kinetic profiling of positive allosteric modulators of the mGlu2 receptor
Supervisor: Maarten Doornbos
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Thomas Schmidt Lab (Single Molecule Microscopy)
Intrigued by the way cells autonomously regulate their fate, we strive to understand and visualize cellular processes as the basis of Cell Signaling.
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Monitoring Alzheimer's disease in transgenic mice with ultra high field magnetic resonance imaging
Promotor: H.J.M. de Groot, Co-Promotor: A. Alia
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Cannabinoid receptor 2 as a ‘drugable’ target: kinetic profile of novel receptor ligands
Supervisor: Andrea Martella
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In Vivo Biomechanics of Cruciate Ligament Injuries
PhD Defence
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Novel Hollow Microneedle Technology for Depth-Controlled Microinjection-Mediated Dermal Vaccination: A Study with Polio Vaccine in Rats
PURPOSE: The aim of the study was to develop a cheap and fast method to produce hollow microneedles and an applicator for injecting vaccines into the skin at a pre-defined depth and test the applicability of the system for dermal polio vaccination.
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Monitoring the penetration process of single microneedles with varying tip diameters
Microneedles represent promising tools for delivery of drugs to the skin. However, before these microneedles can be used in clinical practice, it is essential to understand the process of skin penetration by these microneedles.
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Development of a universal delivery system for tailor-made cancer vaccines
The potential of liposomal cancer vaccines
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Time is of the essence: investigating kinetic interactions between drug, endogenous neuropeptides and receptor
Promotor: A.P. IJzerman Co-promotor: L.H. Heitman
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Magnetic Resonance Imaging of the Adult Zebrafish
Zebrafish is an excellent model organism for studying various human diseases. Due to opaqueness of the adult phase, in vivo studies are restricted to early embryonic stages. This raises the need for rapid sensitive and non-invasive in vivo imaging methods to follow developmental processes, not only…
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Resistance to PARP inhibition by DNA damage response alterations in BRCA1/2-deficient tumors
Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.
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Reverse engineering of drug induced QT(c) interval prolongation: Towards a systems pharmacology approach
Promotor: M. Danhof Co-promotor: O.E. Della Pasqua
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Polyfluorinated bis-styrylbenzenes as amyloid-beta plaque binding ligands
Detection of cerebral beta-amyloid (Abeta) by targeted contrast agents remains of great interest to aid the in vivo diagnosis of Alzheimer's disease (AD). Bis-styrylbenzenes have been previously reported as potential Abeta imaging agents.
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Advanced in vitro models for studying drug induced toxicity
Promotor: Prof.dr. B. van de Water, Co-promotor: L.S. Price
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Bioactivity based quality control for Chinese herbal medicine
Can we establish a new quality control system for herbal medicines that is based on bioactivity rather than a few abundant chemicals?
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SysMedPD: Systems Medicine of Mitochondrial Parkinson's Disease
The overall objective of this project is to identify novel drug candidates that are capable of slowing down the progression of neurodegeneration in the subset of Parkinson’s disease (PD) patients with overt mitochondrial dysfunction. Multimodal phenotypic characterisation of cohorts of monogenic PD…
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Cationic liposomes loaded with a synthetic long Peptide and poly(i:C): a defined adjuvanted vaccine for induction of antigen-specific T cell
For effective cancer immunotherapy by vaccination, co-delivery of tumour antigens and adjuvants to dendritic cells and subsequent activation of antigen-specific cytotoxic T cells (CTLs) is crucial. In this study, a synthetic long peptide (SLP) harbouring the model CTL epitope SIINFEKL was encapsulated…
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Using insertional mutagenesis to identify breast cancer drivers and therapy resistance genes in mice
PhD Defence
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Unravelling cancer drug resistance mechanisms
Mechanisms fro drug resistance
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Research
Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…
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Fundamental and translational medical biochemistry
Through metabolism, biochemical processes give rise to the complexity of life. Acquired and inborn errors in metabolism underlie many diseases occurring in man. The challenge for present day medical biochemistry is to find, and integrate, pieces of information at molecular, cell and organismal level…