1,362 zoekresultaten voor “cancer drug discovery initiative” in de Publieke website
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Cancer Drug Discovery Initiative maakt nieuwe therapieën tegen kanker mogelijk
Het Antoni van Leeuwenhoek/Nederlands Kanker Instituut, het Leids Instituut voor de Chemie en het Pivot Park Screening Centre gaan kennis en infrastructuur delen in het Cancer Drug Discovery Initiative. Vrijdag 11 oktober tekenden ze een letter of intent.
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Discovery of BUB1 kinase inhibitors for the treatment of cancer
The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.
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Modern Drug Discovery
How are new drugs developed? This question is central to the Minor Modern Drug Discovery (MDD), which covers the entire trajectory from disease to drug molecule and vice versa. The various research groups involved offer a complementary and interdisciplinary perspective by connecting the diverse subjects…
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Image-based phenotypic screening for breast cancer metastasis drug target discovery
The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.
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Activity-based protein profiling in drug discovery
In the last decades, activity-based protein profiling (ABPP) has emerged as a powerful chemical tool that may aid the ever-challenging drug discovery process.
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Drug Discovery & Safety
In het onderzoeksprogramma Drug Discovery & Safety zijn we geïnteresseerd in de werkzaamheid en veiligheid van nieuwe medicijnen en nieuwe manieren om deze aspecten te bepalen. Daarvoor combineren we geavanceerde imaging en high-throughput screening technieken met computationele aanpakken zoals chem-…
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Exploring Grainyhead-like 2 target genes in breast cancer
The objective of this study was to investigate the expression and function of GRHL2 in different breast cancer subtypes.
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multifaceted roles of Grainyhead-like transcription factor-2 in breast cancer
Breast cancer is the most common cancer in women worldwide. Metastasis, the process by which cancer cells spread to other parts of the body, makes treatments less effective. It is important to unravel the mechanism of metastasis.
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Identification of novel targets in prostate cancer progression
Promotor: B. van de Water, Co-promotor: E.H.J. Danen
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Microengineered Human Blood Vessels For Next Generation Drug Discovery
Heart failure is a major health care problem with high mortality.
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RNA splicing in breast cancer progression
In this thesis, we aimed to better understand the underlying mechanisms involved in TNBC progression and metastasis formation and discover new targets to reduce breast cancer related deaths.
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Cancer chess: molecular insights into PARP inhibitor resistance
The clinical potential of applying synthetic lethality to cancer treatment is famously demonstrated by the BRCA1/PARP1 paradigm: a tumor specific defect in BRCA1 – a component of the DNA double-strand break (DSB) repair pathway homologous recombination (HR) – results in a remarkable sensitivity to PARP1…
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Discovery of antibiotics and their targets in multidrug-resistant bacteria
Global healthcare is on the verge of an antibiotic availability crisis as bacteria have evolved resistance to nearly all known antibacterials. Identifying new antibiotics that operate via novel modes-of-action is therefore of high priority.
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flow of data: connecting large datasets with machine learning in a drug discovery envirionment
This thesis focuses on data found in the field of computational drug discovery. New insight can be obtained by applying machine learning in various ways and in a variety of domains. Two studies delved into the application of proteochemometrics (PCM), a machine learning technique that can be used to…
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BRCA1-associated breast cancer: finding new weapons for an old villain
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Proteins in harmony: Tuning selectivity in early drug discovery
This thesis describes the importance of being able to control the selectivity of potential drug candidates.
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Patient-derived models of breast cancer: a breakthrough story of the duct
To improve treatment of breast cancer patients it is important to understand all stages of breast cancer from initiation to in situ disease and progression to invasive disease. In this thesis we use intraductal injections of patient derived tissue to model ductal carcinoma in situ and invasive breast…
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Discovery of FLT3 inhibitors for the treatment of acute myeloid leukemia
The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.
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Targeted Therapy for Triple-Negative Breast Cancer
The research described in this thesis focused on identifying novel drug targets and synergistic combinations for triple-negative breast cancer (TNBC), a virulent subtype of breast cancer with a dismal prognosis and limited therapeutic options.
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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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Mechanistic modelling of drug target 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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Disrupting the transcriptional machinery to combat triple-negative breast cancer
Triple-negative breast cancer (TNBC) is a subtype of breast cancer characterized by limited treatment options and unfavorable clinical outcomes. Therefore, the research described in this thesis focused on the exploration of novel targeted therapies for TNBC.
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Pulling the strings on anti-cancer immunity
Promotores: J. Jonkers, K.E. de Visser
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genes driving tumorigenesis and therapy resistance in human breast cancer
To improve cancer treatments, personalized medicine approaches have aimed to identify exactly which mutations are driving tumor development in a given patient and specifically target these mutations using precision therapies.
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Uncovering vulnerabilities in triple-negative breast cancer
Triple-negative breast cancer (TNBC) constitutes a small subtype (~15%) of breast cancer, but causes the majority of breast cancer-related deaths.
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Novel regulators of prostate cancer stem cells and tumor aggressiveness
Promotor: R.C.M. Pelger Co-Promotor: G. van der Pluijm
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PI3K signaling and adherens junctions in invasive lobular breast cancer
Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.
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Erik Danen benoemd tot hoogleraar Cancer drug target discovery
Met ingang van 1 april 2018 is Erik Danen benoemd tot hoogleraar Cancer drug target discovery bij het Leiden Academic Centre for Drug Research (LACDR). Zijn vakgebied is celbiologie van kanker, waarin hij zich richt op de achterliggende mechanismen bij uitzaaiingen en resistentie voor behandelingen.
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Harnessing zebrafish xenograft models for ocular melanoma treatment discovery
The aim of this thesis was to develop novel treatment strategies for different types of eye melanoma utilizing zebrafish models. We first establish orthotopic and ectopic xenograft models for uveal and conjunctival melanoma by engraftment of the immortalized cells derived from these tumors into zebrafish…
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Phenotypic screening with 3D cell-based assays
Traditional drug discovery approaches have been hampered by (in vitro) cell-culture models that poorly represent the situation in the human body.
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Klein molecuul gaat uitzaaien tumorcellen tegen
Leidse chemici wisten met collega’s in York en Israël een molecuul te maken dat de weefselstructuur om een tumor heen steviger houdt. Zo kunnen losse tumorcellen niet zo makkelijk uitzaaien. De onderzoekers hebben al patent op het molecuul aangevraagd, maar gebruik hiervan bij patiënten is nog onzeker.…
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Development of novel anti-cancer strategies utilizing the zebrafish xenograft model
In this thesis, we will utilize embryonic zebrafish tumour models to understand the interaction between engrafted human cancer cells and macrophages from the host, test drug administration modalities and anti-cancer efficacies of newly-developed PDT and PACT compounds, and test a light-triggered liposomal…
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Transforming data into knowledge for intelligent decision-making in early drug discovery
Promotor: A.P.IJzerman Co-promotor: A. Bender
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Discovery of Reversible Monoacylglycerol Lipase Inhibitors
Monoacylglycerol lipase (MAGL) is the principal enzyme responsible for hydrolysis of the endocannabinoid 2-arachidonoylglycerol (2-AG). MAGL inhibition provides several potential therapeutic opportunities, including anti-nociceptive, anti-inflammatory and anti-cancer activity.
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The diverse roles of integrin α3β1 in cancer: Lessons learned from skin and breast carcinogenesis
In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer.
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Upconverting nanovesicles for the activation of ruthenium anti-cancer prodrugs with red light
Promotor: E. Bouwman, Co-promotor: S. Bonnet
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Liposome-based synthetic long peptide vaccines for cancer immunotherapy
Promotores: Wim Jiskoot; Ferry Ossendorp
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Discovery of novel inhibitors to investigate diacylglycerol lipases and α/β hydrolase domain 16A
Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt
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Inhibitor discovery of phospholipases and N-acyltransferases
In this thesis an activity-based probe was discovered that could visualize the activity of PLAATs. With an optimized gel-based ABPP assay in hand, screening of a compound library led to the discovery of alpha-ketoamides as a hit for PLAAT3.
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Disease, Signaling and Drug Targets
The Minor Computational Approaches to Disease, Signaling and Drug Targets (CADSDT) is focused on fundamental scientific research required for discovery of new drug targets and development of new drugs.
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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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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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Getting personal: Advancing personalized oncology through computational analysis of membrane proteins
Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.
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The good? The bad? The mutant! Characterization of cancer-related somatic mutations and identification of a selectivity hotspot in adenosine
G protein-coupled receptors (GPCRs), one of the largest families of membrane proteins, are responsive to a diverse set of physiological endogenous ligands including hormones and neurotransmitters.
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To explore the drug space smarter: Artificial intelligence in drug design for G protein-coupled receptors
Over several decades, a variety of computational methods for drug discovery have been proposed and applied in practice. With the accumulation of data and the development of machine learning methods, computational drug design methods have gradually shifted to a new paradigm, i.e. deep learning methods…
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Using Liposomes; Opportunities for Treatment of Atherosclerosis and Cancer
This thesis focuses on using liposomes in two different treatment strategies; vaccination (or immunotherapy) and delivery of a small molecule, and in two different disease models; cancer and atherosclerosis.
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Photo-activated drug delivery systems
O-Nitrobenzyl groepen worden veel gebruikt als moleculaire beschermgroepen die je met licht kunt verwijderen.
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PLGA-based particulate vaccine delivery systems for immunotherapy of cancer
Promotores: W. Jiskoot, F. Ossendorp
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Discovery of selective diacylglycerol lipase β inhibitors
Diacylglycerol lipases (DAGLα and DAGLβ) are responsible for the biosynthesis of the endocannabinoid 2-arachidonoylglycerol (2-AG) in the brain and peripheral tissues. Selective DAGLβ inhibitors have been proposed as a potential treatment for inflammatory diseases with reduced potential for central…
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Cell-autonomous and host-dependent CXCR4 signaling in cancer metastasis: insights from a zebrafish xenograft model
Promotor: A.H. Meijer, Co-promotor: B.E. Snaar-Jagalska