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Childhood obesity is an increasing health issue. In the first part of this thesis comorbidities in children with obesity were studied, concerning the diagnostic process and dosing regimens.

Promotores: B. van de Water; P. Hogendoorn; J. Bovée Co-Promotor: E.H.J. Danen

Promotors: C.A.J. Knibbe, Anthonius de Boer, Co-promotor: M.M.J. van der Vorst

Sepsis is a life-threatening condition caused by a dysregulated host response to infection, it is associated with significant morbidity, mortality, and with a high financial burden on global healthcare systems. Bacterial infections are the primary cause of sepsis, but the growing prevalence of antimicrobial…

Tuberculosis (TB) is associated with 1.5 million deaths annually. There is a need exists to optimize both current as well as novel antibiotic combination treatment strategies to improve the effectiveness and safety of treatments against TB.

Cardiovascular diseases are the primary cause of death in the world with atherosclerosis as primary underlying cause.

Fungal infections pose a significant threat to individuals with compromised immune systems and despite advancements in diagnosis and treatment, they continue to jeopardize patient’s health.

The spindle-assembly checkpoint (SAC) is a safety mechanism which secures accurate chromosome segregation during mitosis.

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.

Exploring metabolomics-based biomarkers for diagnosis and treatment response monitoring of community-acquired pneumonia

The disease acute myeloid leukemia (AML) is characterized by fast progression and low survival rates.

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…

This thesis represents a comprehensive investigation into the control of cancer stemness and metastatic initiation using a combination of advanced zebrafish xenograft models and in vitro assays.

Lipid signaling is an essential biological event/process in a plethora of pathophysiological conditions. The underlying idea of this thesis is that many of the roles and the complex interplay of the individual signaling lipids in inflammatory processes and related conditions in health and disease is…

M. Danhof, Co-promotores: J. Freijer, A. Yassen

The bacterial cell wall is a nearly universal structure that offers protection and gives the cell its shape. However, environmental stressors, such as cell wall-targeting antibiotics and hyperosmotic conditions, can induce bacteria to shift to a wall-deficient state. It is unknown whether the lack of…

Breast cancer (BC) is a clinically and biologically heterogeneous disease.

In this thesis, we aim to shed light on the diverse and often opposing roles of integrin α3β1 in cancer.

Explaining treatment response variability between and within patients can support treatment and dosing optimization, to improve treatment of individual patients.

The effective treatment of tuberculosis (TB) remains a major challenge to global health.

Antimicrobial drugs constitute a fundamental part of modern medicine. The global rise in antimicrobial resistance poses a major threat to global health.

Promotor: Prof.dr. J. Kuiper

Promotor: H.S. Overkleeft, Co-promotor: M. van der Stelt

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.

Cardiovascular disease is the number one cause of death worldwide. The most important risk factor for developing this disease is high cholesterol levels in the blood.

Real-life processes are characterized by dynamics involving time. Examples are walking, sleeping, disease progress in medical treatment, and events in a workflow.

Neurodegenerative diseases, including Parkinson’s disease (PD), are increasing in prevalence due to the aging population. Despite extensive study, these diseases are still not fully understood and the lack of personalised treatment options that can target the cause of the diseases, rather than the symptoms,…

In this PhD-thesis several new and existing data science application are described that are particularly focused on applications for tax administrations.

Kidney transplantation is a major advance of modern medicine. This course will give you state of the art updates about what used to be an experimental, risky, and very limited treatment option more than 50 years ago and is now routinely performed in many countries worldwide.

Nederland heeft afgelopen week de nationale terrorismelijst uitgebreid: tien Nederlanders zijn aan deze lijst toegevoegd. Dit heeft onder andere gevolgen voor hun financiële middelen, maar is dit middel wel effectief? En wat als je onterecht op deze lijst terecht komt? De NOS sprak hierover met Jelle…

In Nederland zijn er ongeveer 36.000 zeer makkelijk lerende kinderen in de basisschoolleeftijd. Hoe zorg je er als school voor dat zij niet in de knel komen?

This thesis focuses on the development of sample-preparation methods for small amounts of samples and applying the developed methods to muscle tissues to investigate the mechanisms involved in sarcopenia.

Hoe meer we leren over een (neuro-)psychologische of lichamelijke aandoening en de hieraan gerelateerde gedragsfactoren, hoe beter we deze niet alleen kunnen signaleren, maar ook behandelen. Het is dus belangrijk dat recente inzichten over (neuro-)psychologische problemen en daaraan gerelateerde gedragsfactoren…

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…

The research described in this thesis has, using the zebrafish as a model system, shed new light on the intricate relationship between TB and DM2, in particular on the role of leptin, SHP-1 and glucocorticoids.

Om de juiste klinische beslissingen te nemen of effectieve diagnostische testen en behandelingen te kunnen ontwikkelen, is het belangrijk om de onderliggende mechanismen van een aandoening of een bepaald gedrag te begrijpen.

Als een nieuwe methode is ontwikkeld om een (neuro-)psychologische aandoening of hieraan gerelateerde gedragsfactoren te herkennen en te behandelen, kan deze nog niet direct in de klinische praktijk worden ingezet. Eerst moet de methode geëvalueerd worden, bij voorkeur in gerandomiseerde, gecontroleerde…

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.

Extending our current arsenal of antibiotics is key to staying ahead in the arms race between humans and resistant bacteria.

The impact of the phenotypic plasticity of P. aeruginosa and the distinct CF lung microenvironments on antibiotic drug effects and resistance remains poorly understood.

De effecten van veel behandelingen worden in belangrijke mate bepaald door andere factoren dan het geneesmiddel of de behandeling zelf. Zo kunnen placebo-effecten even groot zijn als het effect van bijvoorbeeld antidepressiva of pijnstillers. Factoren die hieraan bijdragen zijn het vertrouwen in de…

The main aim of my Ph.D. thesis is to further explore the value of using early developing zebrafish larvae (up to 5 dpf) as a model to study anxiety-like behaviour and their pharmacological modulation with drugs.

In photoactivated chemotherapy (PACT), a biologically active compound is caged by a light-cleavable protecting group.

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