A5032559601- Cancer, Hypoxia, and Metabolism
- Glioma Diagnosis and Treatment
- Cancer Research and Treatments
- Nanoplatforms for cancer theranostics
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- Amino Acid Enzymes and Metabolism
- Autophagy in Disease and Therapy
- Cancer Cells and Metastasis
- Extracellular vesicles in disease
- Medical Imaging Techniques and Applications
- RNA modifications and cancer
- Ferroptosis and cancer prognosis
- Virus-based gene therapy research
- Cancer-related Molecular Pathways
- Retinoids in leukemia and cellular processes
- Brain Metastases and Treatment
- Advanced Proteomics Techniques and Applications
- Neurogenesis and neuroplasticity mechanisms
- Cell Image Analysis Techniques
- Cancer-related gene regulation
- Acute Lymphoblastic Leukemia research
- Protist diversity and phylogeny
- Acute Myeloid Leukemia Research
- Cerebrovascular and genetic disorders
Maastricht University
2015-2025
Maastro Clinic
2015-2025
Maastricht University Medical Centre
2019-2024
Glioblastoma multiforme (GBM) is the most common malignant brain tumor in adults. The current standard of care includes surgery followed by radiotherapy (RT) and chemotherapy with temozolomide (TMZ). Treatment often fails due to radiation resistance intrinsic or acquired TMZ a small percentage cells stem cell-like behavior (CSC). NOTCH signaling pathway expressed active human glioblastoma inhibitors attenuate growth vivo xenograft models. Here we show using an image guided micro-CT precision...
The hypoxia-inducible transcription factors (HIF)-1/2α are the main oxygen sensors which regulate adaptation to intratumoral hypoxia. aim of this study was assess role HIF proteins in regulating radiation response a non-small cell lung cancer (NSCLC) vitro model. To directly unique and overlapping functions HIF-1α HIF-2α, we use CRISPR gene-editing generate isogenic H1299 carcinoma cells lacking HIF-1α, HIF-2α or both. We found that HIF1 knockout cells, strongly induced by hypoxia compared...
In the last decade, advancements in understanding genetic landscape of lung squamous cell carcinoma (LUSC) have significantly impacted therapy development. Immune checkpoint inhibitors (ICI) shown great promise, improving overall and progression-free survival approximately 25% patients. However, challenges remain, such as lack predictive biomarkers, difficulties patient stratification, identifying mechanisms that cancers use to become immune-resistant (“immune-cold”). Analysis TCGA datasets...
Hypoxia is a common feature of solid tumors and associated with increased tumor progression, resistance to therapy metastasis. Hence, hypoxia prognostic factor independent treatment modality. To survive hypoxia, cells activate macroautophagy/autophagy. Paradoxically, in several cancer types, mutations or loss essential autophagy genes have been reported that are earlier onset growth. However, our knowledge, the phenotypic therapeutic consequences deficiency remained unexplored. In this...
Background Lung cancer is the leading cause of death worldwide. More effective treatments are needed to increase durable responses and prolong patient survival. Standard care treatment for patients with non-operable stage III-IV NSCLC concurrent chemotherapy radiation. An activated NOTCH signaling pathway associated poor outcome resistance in non-small-cell lung (NSCLC). pharmacological small molecule inhibitors have been blocking tumor growth enhancing effects preclinical models. However, a...
Hypoxia is a common feature of solid tumours and activates adaptation mechanisms in cancer cells that induce therapy resistance has profound effects on cellular metabolism. As such, hypoxia an important contributor to progression associated with poor prognosis. Metabolic alterations within the tumour microenvironment support growth via, amongst others, suppression immune reactions induction angiogenesis. Recently, extracellular vesicles (EV) have emerged as mediators intercellular...
ABSTRACT Intratumoural hypoxia is a common characteristic of malignant treatment-resistant cancers. However, hypoxia-modification strategies for the clinic remain elusive. To date, little known on behaviour individual hypoxic tumour cells in their microenvironment. explore this issue spatial and temporally controlled manner, we developed genetically encoded sensor by fusing O2-labile hypoxia-inducible factor 1α (HIF-1α) protein to eGFP tamoxifen-regulated Cre recombinase. Under normoxic...
Background and purposeHypoxia is a common feature of tumours, associated with poor prognosis due to increased resistance radio- chemotherapy enhanced metastasis development. Previously we demonstrated that GABARAPL1 required for the secretion extracellular vesicles (EV) pro-angiogenic properties during hypoxia. Here, explored role GABARAPL1+ EV in metastatic cascade.Materials methodsGABARAPL1 deficient or control MDA-MB-231 cells were injected murine mammary fat pads. Lungs dissected...
Abstract Glioblastoma multiforme (GBM) is the most common and malignant brain tumor in adults. Aggressive multimodal treatment using surgery followed by radiotherapy chemotherapy extends median survival of GBM patients to approximately one year after diagnosis. Treatment not curative because intrinsic acquired radiation resistance a subpopulation cells. Notch inhibition has been shown impair tumorigenic capacity these cells as well enhance their sensitivity towards radiation. Therefore, we...
Abstract Intratumoural hypoxia is a common characteristic of malignant treatment-resistant cancers. However, hypoxia-modification strategies for the clinic remain elusive. To date little known on behaviour individual hypoxic tumour cells in their microenvironment. explore this issue spatial and temporally-controlled manner we developed genetically encoded sensor by fusing O 2 -labile Hypoxia-Inducible Factor 1α to eGFP tamoxifen-regulated Cre recombinase. Under normoxic conditions HIF-1α...
S107 ______________________________________________________________________________________________________not able to form new tumors and have high expression of CD127 on their T cells, a marker for immunological memory.This treatment will be further investigated in Phase I study patients with an oligometastatic solid tumor (NCT02086721).
Introduction Hypoxia plays a role in many types of cancer, and is linked to metastasis, genetic instability, resistance therapy poor prognosis. Hypoxic modification has been tested clinical trials, but results have inconclusive, part due knowledge gap into the characterisation behaviour hypoxic tumour cells. In this project, cells will be lineage traced investigate their dissemination within primary for presence circulating distant metastasis. To contribution fraction resistance,...
Introduction Lung cancer is the leading cause of death in western countries. While significant progress has been made terms treatment, radiotherapy limited by dose-limiting side-effects. Reducing side-effects may improve tumour control dose-escalation and treatment-time. The NOTCH signalling pathway plays an important role differentiation airway epithelium its deregulation associated with lung cancer. However, mechanism which inhibition integrates repair unknown. What currently lacking are...
ABSTRACT Introduction T-cell acute lymphoblastic leukaemia (T-ALL) is an aggressive cancer arising from progenitors. Although current treatments, including chemotherapy and glucocorticoids, have significantly improved survival, T-ALL remains a fatal disease new treatment options are needed. Since more than 60% of cases bear oncogenic NOTCH1 mutations, inhibitors signalling being actively investigated for the T-ALL. However, they limited efficacy in tumours due to dose-limiting toxicities....