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.

Promotor: Prof.dr. J. Kuiper

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…

The last decades it is increasingly recognized that acute as well as chronic postoperative pain is an important problem. Treatment and prevention of postoperative pain is a challenge, especially in special patient populations where there is only limited guidance on how to optimally use opioids.

Promotor: C.A.J. Knibbe, Co-promotores: H.P.A. van Dongen, B. van Ramshorst

Dissolving microneedles are a subgroup of microneedle types that completely dissolve within the skin. During this dissolving process the vaccine, stored in the needle matrix, is released into the skin.

Promotor: G.F.A. Kersten, W. Jiskoot, Co-promotor: B. Metz

Promotor: J. A. Bouwstra

Promotor: Thomas Hankemeier, Co-promotores: Heiko van der Linden, Paul Vulto

Drug-induced liver injury (DILI) is one of the main reasons for drug attrition during pre-clinical and clinical phases of drug development as well as for drug withdrawal post-marketing.

The main aim of this thesis was to unravel the signaling and regulatory networks that drive tumor cell migration during breast cancer metastasis.

The adenosine receptors are proteins that reside in the extracellular membranes of cells. Activation of adenosine receptors plays a role in many physiological and pathological processes, such as immune responses and cancers.

Promotor: Prof.dr. B. van de Water, Co-promotores: L.T.M. van der Ven, A.S. Kienhuis

This thesis tackles the difficulty of predicting the liver’s clinical response to novel therapies, a challenge arising from interspecies differences and limitations of existing in vitro models.

Promotor: J. Kuiper

Promotor: Prof.dr. T. Hankemeier, Prof.dr. J.C.T. Eijkel (Twente University)

Pancreatic ductal adenocarcinoma (PDAC) is among the cancers with the highest mortality rate, despite a relatively low incidence.

Preterm birth is a major contributor to neonatal morbidity and mortality and is associated with both acute complications and long-term health consequences.

Promotores: W. Jiskoot, F. Ossendorp

Atherosclerosis is a progressive disease resulting in the formation of an arterial plaque. Despite lipid lowering, recurrent cardiovascular events remain a risk. While atherosclerosis is primarily lipid-driven, the immune system plays a critical role in the pathophysiology.

The aim of this thesis is to expedite and ensure the systematic accuracy of clearance scaling from adults to paediatric patients, with a special focus on drugs undergoing hepatic metabolism.

This thesis aims to develop model-based approaches to optimize drug dosing in patients with overweight and (morbid) obesity.

In this thesis the links between allergy and intestinal health, the gut microbiome (GM), and external factors were studied by exploring the metabolome in longitudinal clinical studies and in vitro models.

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

Drug development critically depends on preclinical models that mimic human physiology, yet traditional two-dimensional cultures and animal models often lack predictive power.

In dit proefschrift onderzochten we hoe we kankerbehandelingen slimmer en veiliger kunnen doseren. Veel middelen worden nog volgens een “one size fits all”-schema gegeven, vaak gebaseerd op de maximaal verdraagbare dosis. Dat kan leiden tot onnodig veel bijwerkingen, behandelingonderbrekingen en hoge…

Als gevolg van de grote technologische vooruitgang in de gezondheidszorg worden in toenemende mate gegevens verzameld tijdens de uitvoering van klinische onderzoeken.

The overarching clinical aim of this thesis was to improve pharmacological pain management by characterizing the pharmacodynamics of analgesics. This promotion has been awarded the predicate cum laude.

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

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.

Promotor: A.P. IJzerman

The major and ultimate aim of metabolomics is to obtain an answer to a specific biological or clinical question.

Promotor: B. vd Water, T. Schmidt, Co-Promotor: E.H.J. Danen

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…

Promotor: A.P. IJzerman

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…

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).

Promotor: A.P. IJzerman Co-promotor: L.H. Heitman

Nanoparticles can be used as delivery systems for both small molecules and macromolecules such as proteins, peptides or oligonucleotides. This thesis focuses on the use of liposomes, nanometric vesicles formed by a lipid bilayer enclosing an aqueous core. Liposomes are highly versatile delivery syst…

Promotor: Prof.dr. M. Danhof, Co-promotor: O.E. Della Pasqua

In this thesis, mathematical modeling and simulation was applied as a tool to inform quantitative decision making in oncology drug discovery and development.

Discovery and development of Central Nervous System (CNS) drugs is hampered by high attrition rates.

CONCLUSION: This study demonstrates that human macrophages can be induced to exert direct anti-tumor activity against osteosarcoma cells. Our observation that the induction of macrophage anti-tumor activity by L-MTP-PE required IFN-gamma may be of relevance for the optimization of L-MTP-PE therapy in…

Het Gorlaeus Gebouw wordt in drie fasen gerealiseerd. Het nieuwe gebouw is medio 2028 helemaal gereed.

Cholesterol influences many pathways, including serving as precursor for adrenal steroidogenesis. Imbalance of cholesterol levels has been implicated in several diseases including cardiovascular diseases and its underlying pathology, atherosclerosis.

The present thesis focuses on the pharmacological concept of drug-target interaction, which dates back to the beginning of modern pharmacology.

Promotor: J. van der Greef; Co-promotor: E. van Wijk, M. Wang

Promotor: B. van de Water

Promotores: Prof.dr. J. A. Bouwstra, Prof.dr. W. Jiskoot

Promotores: A.P. IJzerman, H.W.T. van Vlijmen