Promotor: A.H. Meijer, Co-promotor: B.E. Snaar-Jagalska

Promotor: R.C.M. Pelger Co-Promotor: G. van der Pluijm

The work in this thesis describes the fundamental role of Lkb1 as a conductor of metabolism-related processes in zebrafish larvae.

Epithelial-mesenchymal plasticity (EMP) and tumor cell migration play an important role in cancer progression, and an improved understanding of the mechanisms underlying these concepts is essential for developing new targeted approaches.

Inactivating mutations in BRCA1 or BRCA2 genes predispose to several types of cancer.

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

Drug development is hampered by the limited predictive value of conventional 2D culture systems, which fail to recapitulate the complexity of the disease microenvironment and contribute to high clinical attrition rates.

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).

This dissertation combines the use of defined microenvironments, high-resolution fluorescence microscopy, and time-resolved analysis, to study intracellular and cellular motility.

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.

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…

Invasive lobular carcinoma (ILC) is the second most common type of breast cancer.

Metastasis is responsible for over 90% of cancer-related deaths and arises from the ability of a small subset of tumor cells to detach from the primary tumor, overcome multiple biochemical and mechanical barriers, disseminate through the body, and colonize distant organs.

Promotor: Prof.dr. B. van de Water

Promotie

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

Despite substantial progress in understanding tuberculosis (TB), the eradication of the TB epidemic is still far from reach.

The molecular mechanisms that instigate a healthy cell to become malignant are fueled by (epi)genetic alterations in so-called driver genes.

Promotores: J. Jonkers, K.E. de Visser

As leading cause of death worldwide, cancer is responsible for nearly 10 million deaths in 2020 according to World Health Organization (WHO). Cisplatin and its derivatives are commonly used chemotherapy agents for current cancer treatment in the clinics.

Optical projection tomography (OPT) is a tomographic 3D imaging technique used for specimens in the millimetre scale.

Cytotoxic T-cells (CTLs) are involved in the clearance of viruses and killing of tumor cells.

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…

Promotor: A. Doelman, Co-promotores: P.J.A. van Heijster; A. Zagaris

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.

Promotor: T. Schmidt, Co-Promotor: B.E. Snaar-Jagalska

Agrobacterium tumefaciens, a gram-negative plant pathogen belonging to the family Rhizobiaceae, is the causative agent of crown gall disease, which can affect many plant species including agronomically important ones.

Cancer is considered the silent pandemic of the 21st century and the second leading cause of death worldwide.

Glycoside hydrolases (glycosidases/GHs) are widely abundant enzymes in all kingdoms of life and are important biocatalysts that catalyze the hydrolysis of glycosidic linkages in oligo/polysaccharides, glycoproteins and glycolipids with tremendous efficiency

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.

Supervisor: P.J.J. Hooykaas

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.

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.

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: E. Bouwman, Co-promotor: S. Bonnet

Bij kanker groeien lichaamscellen ongecontroleerd. Het gedetailleerd in kaart brengen van hoe dit precies gebeurt maakt het mogelijk om efficiënte therapieën te ontwikkelen. Onderzoekers van het Leids Universitair Medisch Centrum (LUMC) en de Universiteit Leiden werken samen aan het vermeerderen van…

Promotie

Promotie

The research presented in this thesis explores the chemotherapeutic potential of metal-based compounds as chemotherapy agents, with an initial focus on the synthesis and DNA interaction studies of platinum and palladium compounds utilizing the [Pt(bapbpy)]2+ scaffold. The study identifies intercalation…

Promotie

Een computer kan veel meer beelden bekijken, en er van leren, dan een menselijke specialist. Voor medische en biologische toepassingen worden AI-systemen in hoog tempo onmisbaar. Ze moeten nog wel leren uitleggen hoe ze tot hun oordeel komen.

Death in all types of melanomas is generally caused by metastasis. Uveal melanoma (UM) is the most common intraocular melanoma, there are currently no (patient-derived) animal models that faithfully recapitulate metastatic dissemination of UM.

This work describes the use of click-to-release chemistry to get spatiotemporal control over immunocytokine activity. Until now, immunocytokines (cytokines coupled to a tumor-targeting-moiety) remained active throughout the body, being able to bind their respective receptors, causing mild to severe…

Prostate cancer (PCa) is one of the most prevalent cancer in males.

Thirty years ago, mutations in the BRCA1 gene were first linked to hereditary breast and ovarian cancer, establishing a genetic basis for cancer development.

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

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

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.